Bruno Charpentier's research while affiliated with French National Centre for Scientific Research and other places
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Publications (86)
Chemical cross-linking reactions (XL) are an important strategy for studying protein-protein interactions (PPIs), including low abundant sub-complexes, in structural biology. However, choosing XL reagents and conditions is laborious and mostly limited to analysis of protein assemblies that can be resolved using SDS-PAGE. To overcome these limitatio...
The Prader–Willi/Angelman syndrome (PWS/AS) locus is regulated by the epigenetic mechanism of parental genomic imprinting. This region holds two eutherian-specific, large tandem repeats of box C/D small nucleolar RNA (Snord) genes called SNORD115 and SNORD116, whose loss of paternal expression is key in the development of the PWS. Snords represent...
Mass photometry (MP) is a versatile, fast and low sample-consuming biophysical technique that gained interest in structural biology to study noncovalent assemblies in native conditions. We report here on a novel method to perform MP analysis in denaturing conditions (dMP) and its application for fast, accurate and straightforward optimization of ch...
Mass photometry (MP) is a versatile, fast and low sample-consuming biophysical technique that gained interest in structural biology to study noncovalent assemblies in native conditions. We report here on a novel method to perform MP analysis in denaturing conditions (dMP) and its application for fast, accurate and straightforward optimization of ch...
DPCD is a protein that may play a role in cilia formation and whose absence leads to primary ciliary dyskinesia (PCD), a rare disease caused by impairment of ciliated cells. Except for high-throughput studies that identified DPCD as a possible RUVBL1 (R1) and RUVBL2 (R2) partner, no in-depth cellular, biochemical, and structural investigation invol...
MicroRNAs silence mRNAs by guiding the RISC complex. RISC assembly occurs following cleavage of pre-miRNAs by Dicer, assisted by TRBP or PACT, and the transfer of miRNAs to AGO proteins. The R2TP complex is an HSP90 co-chaperone involved in the assembly of ribonucleoprotein particles. Here, we show that the R2TP component RPAP3 binds TRBP but not P...
The eutherian-specific SNORD116 family of repeated box C/D snoRNA genes is suspected to play a major role in the Prader Willi syndrome (PWS), yet its molecular function remains poorly understood. Here, we combined phylogenetic and molecular analyses to identify candidate RNA targets. Based on the analysis of several eutherian orthologs, we found ev...
Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we prese...
Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins initiates co-transcriptionally and requires the action of the assembly machinery including the Hsp90/R2TP complex, the Rsa1p:Hit1p heterodimer and the Bcd1 protein. We present genetic interactions between the Rsa1p-encoding gene and genes involved in chromatin organization includin...
The PAQosome is a large complex composed of the HSP90/R2TP chaperone and a prefoldin-like module. It promotes the biogenesis of cellular machineries but it is unclear how it discriminates closely related client proteins. Among the main PAQosome clients are C/D snoRNPs and in particular their core protein NOP58. Using NOP58 mutants and proteomic exp...
MicroRNAs silence mRNAs by guiding the RISC complex. RISC assembly requires cleavage of pre-miRNAs by Dicer, assisted by TRBP or PACT, and the transfer of miRNAs to AGO proteins. The R2TP complex is an HSP90 cochaperone involved in the assembly of ribonucleoprotein particles. Here, we show that the R2TP component RPAP3 binds TRBP but not PACT. Spec...
Non-coding RNAs associate with proteins to form ribonucleoproteins (RNPs), such as ribosome, box C/D snoRNPs, H/ACA snoRNPs, ribonuclease P, telomerase and spliceosome to ensure cell viability. The assembly of these RNA-protein complexes relies on the ability of the RNA to adopt the correct bound conformation. K-turn motifs represent ubiquitous bin...
Biogenesis of eukaryotic box C/D small nucleolar ribonucleoproteins (C/D snoRNPs) is guided by conserved trans-acting factors that act collectively to assemble the core proteins SNU13/Snu13, NOP58/Nop58, NOP56/Nop56, FBL/Nop1, and box C/D small nucleolar RNAs (C/D snoRNAs), in human and in yeast, respectively. This finely elaborated process involve...
We report the nearly complete ¹H, ¹⁵N and ¹³C resonance assignment and the solution structure of the external DII domain of the yeast Rvb2 protein, a member of the AAA+ATPase superfamily.
Archaeal RNA:pseudouridine-synthase (PUS) Cbf5 in complex with proteins L7Ae, Nop10
and Gar1, and guide box H/ACA sRNAs forms ribonucleoprotein (RNP) catalysts that insure
the conversion of uridines into pseudouridines (Ψs) in ribosomal RNAs (rRNAs).
Nonetheless, in the absence of guide RNA, Cbf5 catalyzes the in vitro formation of Ψ2603 in Pyro...
RPAP3 and PIH1D1 are part of the HSP90 co-chaperone R2TP complex involved in the assembly process of many molecular machines. In this study, we performed a deep structural investigation of the HSP binding abilities of the two TPR domains of RPAP3. We combined 3D NMR, non-denaturing MS, and ITC techniques with Y2H, IP-LUMIER, FRET, and ATPase activi...
R2TP is an HSP90 co-chaperone that assembles important macro-molecular machineries. It is composed of an RPAP3-PIH1D1 heterodimer, which binds the two essential AAA+ATPases RUVBL1/RUVBL2. Here, we resolve the structure of the conserved C-terminal domain of RPAP3, and we show that it directly binds RUVBL1/RUVBL2 hexamers. The human genome encodes tw...
Objective
Decreased expression of collagen type II in favour of collagen type I or X is one hallmark of chondrocyte phenotype changes in osteoarthritic (OA) cartilage. MicroRNA- (miR-) 29b was previously shown to target collagens in several tissues. We studied whether it could contribute to collagen imbalance in chondrocytes with an impaired phenot...
The U3 box C/D snoRNA is one key element of 90S pre-ribosome. It contains a 5΄ domain pairing with pre-rRNA and the U3B/C and U3C΄/D motifs for U3 packaging into a unique small nucleolar ribonucleoprotein particle (snoRNP). The RNA-binding protein Snu13/SNU13 nucleates on U3B/C the assembly of box C/D proteins Nop1p/FBL and Nop56p/NOP56, and the U3...
Main demographic features of the OA or non-OA patients whose cartilage samples were used as primary sources of articular chondrocytes.
Box C/D small nucleolar ribonucleoparticles (snoRNPs) support 2'-O-methylation of several target RNAs. They share a common set of four core proteins (SNU13, NOP58, NOP56, and FBL) that are assembled on different guide small nucleolar RNAs. Assembly of these entities involves additional protein factors that are absent in the mature active particle....
The Sm proteins are loaded on snRNAs by the SMN complex, but how snRNP-specific proteins are assembled remains poorly characterized. U4 snRNP and box C/D snoRNPs have structural similarities. They both contain the 15.5K and proteins with NOP domains (PRP31 for U4, NOP56/58 for snoRNPs). Biogenesis of box C/D snoRNPs involves NUFIP and the HSP90/R2T...
In all organisms, several distinct stand-alone pseudouridine synthase (PUS) family enzymes are expressed to isomerize uridine into pseudouridine (Ψ) by specific recognition of RNAs. In addition, Ψs are generated in Archaea and Eukaryotes by PUS enzymes which are organized as ribonucleoprotein particles (RNP)-the box H/ACA s/snoRNPs. For this modifi...
The box H/ACA small ribonucleoprotein particles (H/ACA sRNPs) are RNP enzymes that isomerize uridines (U) into pseudouridines (Ψ) in archaeal RNAs. The RNA component acts as a guide by forming base-pair interactions with the substrate RNA to specify the target nucleotide of the modification to the catalytic subunit Cbf5. Here, we have analyzed asso...
Site-specific isomerization of uridines into pseudouridines in RNAs is catalyzed either by stand-alone enzymes or by box H/ACA ribonucleoprotein particles (sno/sRNPs). The archaeal box H/ACA sRNPs are 5-component complexes that consist of a guide RNA and the aCBF5, aNOP10, L7Ae and aGAR1 proteins. In this study, we performed pairwise incubations of...
In vitro, assembly of box C/D small nucleolar ribonucleoproteins (snoRNPs) involves the sequential recruitment of core proteins to snoRNAs. In vivo, however, assembly factors are required (NUFIP, BCD1, and the HSP90-R2TP complex), and it is unknown whether a similar sequential scheme applies. In this paper, we describe systematic quantitative stabl...
Biogenesis of eukaryotic box C/D small nucleolar ribonucleoprotein particles (C/D snoRNPs) involves conserved trans-acting factors, which are proposed to facilitate the assembly of the core proteins Snu13p/15.5K, Nop58p/NOP58, Nop56p/NOP56
and Nop1p/Fibrillarin on box C/D small nucleolar RNAs (C/D snoRNAs). In yeast, protein Rsa1 acts as a platform...
Osteoarthritis (OA) is a whole-joint disease characterized by cartilage degradation and mineralization associated with chondrocyte phenotype changes, subchondral bone sclerosis and mild synovial inflammation. The extracellular levels of inorganic phosphate (ePi) and pyrophosphate (ePPi) are major regulators of the mineralization process but also pl...
Post-transcriptional RNA modification is a universally conserved and highly complex metabolic process in the living cell. To date, over 110 chemically different modifications have been identified and characterized in cellular RNA species, and all of these are formed by a highly specific enzymatic machinery which recognizes and modifies RNA targets....
We report the nearly complete (1)H, (15)N and (13)C resonance assignments of the two tetratricopeptide-repeat domains of the human RPAP3 protein, a co-chaperone of the heat-shock protein family.
We report the nearly complete (1)H, (15)N and (13)C resonance assignment of the complex formed by the C-terminal domains of Pih1 and Tah1 from S. cerevisiae and evidence the folding ability of Tah1 under complex formation.
The yeast Snu13p protein and its 15.5K human homolog both bind U4 snRNA and box C/D snoRNAs. They also bind the Rsa1p/NUFIP assembly factor, proposed to scaffold immature snoRNPs and to recruit the Hsp90-R2TP chaperone complex. However, the nature of the Snu13p/15.5K-Rsa1p/NUFIP interaction and its exact role in snoRNP assembly remained to be eluci...
The ubiquitous Hsp90 chaperone participates in snoRNP and RNA polymerase assembly through interaction with the R2TP complex. This complex includes the proteins Tah1, Pih1, Rvb1, and Rvb2. Tah1 bridges Hsp90 to R2TP. Its minimal TPR domain includes two TPR motifs and a capping helix. We established the high-resolution solution structures of Tah1 fre...
Effect of mutations in protein aNOP10 on the rate of Ψ55 modification by aCBF5 in tRNA. (A) Secondary structure models of P. abyssi tRNAAsp. Residue U55 is circled. The CCA sequence at the 3′ end is boxed. The CCA deletion in variants tRNAAsp-ΔCCA is shown. (B) Time course analysis of Ψ55 formation in tRNA. The tRNAAsp−ΔCCA substrate was radiolabel...
Average h-Twist versus time of the two RNA hairpin models Pab21P1 and Pab91P1. The plotted values are calculated by averaging the helical twist on the nine base-pairs of P1. The plots are annotated by indication of the average values of the buckle during the simulation between Pab21P1 (red) and Pab91P1 (blue). The histograms are also annotated by i...
Chemical probing of sub-complexes formed by the association of L7Ae with various sRNA. (A and C) Secondary structure models of P. abyssi Pab19 and Pab160 sRNAs. (B and D) Footprinting of protein L7Ae (L) on the various sRNAs. Reactions with lead were carried out on 5′-32P end-labeled sRNA as in Figure 3. Samples were fractionated on 10% polyacrylam...
Effect of mutations in proteins L7Ae and aNOP10 on substrate RNA positioning within the sRNP. The fluorescence intensity at 366 nm was monitored while the substrate RNA labeled with both 5-FU and 2-AP bound with the Pab21 guide RNA was first titrated with saturating amounts of the sRNP proteins. All proteins were present at 5× molar excess relative...
Multiple RNA-guided pseudouridine synthases, H/ACA ribonucleoprotein particles (RNPs) which contain a guide RNA and four proteins, catalyze site-specific post-transcriptional isomerization of uridines into pseudouridines in substrate RNAs. In archaeal particles, the guide small RNA (sRNA) is anchored by the pseudouridine synthase aCBF5 and the ribo...
Controlling iron homeostasis is crucial for all aerobically grown living cells that are exposed to oxidative damage by reactive oxygen species (ROS), as free iron increases the production of ROS. Methionine sulfoxide reductases (Msr) are key enzymes in repairing ROS-mediated damage to proteins, as they reduce oxidized methionine (MetSO) residues to...
Western blot analysis of MsrB protein levels from cells expressing wild type msrB and mutant msrB. Wild type msrB (A) and mutant msrB (mut2a (B) and mut2b (C)). Strains were grown at 37°C to an O.D.600 of 0.4. After 60 min of incubation with 2,2’dip, samples were removed and proteins were extracted as described in Materials and Methods. MsrB protei...
Box C/D small nucleolar Ribonucleoproteins (C/D snoRNPs)
are essential complexes for gene expression as they direct
FEBS Journal 280 (Suppl. 1) (2013) 3–617
ª 2013 The Authors. FEBS Journal ª 2013 FEBS 33
SW01 Mechanisms of Genetic Control Abstracts
post-transcriptional modifications of rRNAs in the nucleolus.
Box C/D snoRNAs are assembled with a s...
How far do H/ACA sRNPs contribute to rRNA pseudouridylation in Archaea was still an open question. Hence here, by computational
search in three Pyrococcus genomes, we identified seven H/ACA sRNAs and predicted their target sites in rRNAs. In parallel, we experimentally identified
17 Ψ residues in P. abyssi rRNAs. By in vitro reconstitution of H/ACA...
RNA-binding proteins of the L7Ae family are at the heart of many essential ribonucleoproteins (RNPs), including box C/D and H/ACA small nucleolar RNPs, U4 small nuclear RNP, telomerase, and messenger RNPs coding for selenoproteins. In this study, we show that Nufip and its yeast homologue Rsa1 are key components of the machinery that assembles thes...
Whereas dedicated computational approaches have been developed for the search of C/D sRNAs and snoRNAs, as yet no dedicated computational approach has been developed for the search of archaeal H/ACA sRNAs. Here we describe a computational approach allowing a fast and selective identification of H/ACA sRNAs in archaeal genomes. It is easy to use, ev...
Conditions for the reconstitution of archaeal sRNPs active in RNA-guided posttranscriptional modification of RNAs (2'-O-methylation or pseudouridylation) were recently developed. This has opened a vast field of research on structure-function relationships of the sRNP components. We present here an efficient method for in vitro reconstitution of H/A...
Protein aNOP10 has an essential scaffolding function in H/ACA sRNPs and its interaction with the pseudouridine(Ψ)-synthase aCBF5 is required for the RNA-guided RNA:Ψ-synthase activity. Recently, aCBF5 was shown to catalyze the isomerization of U55 in tRNAs without the help of a guide sRNA.
Here we show that the stable anchoring of aCBF5 to tRNAs re...
In archaeal rRNAs, the isomerization of uridine into pseudouridine (Ψ) is achieved by the H/ACA sRNPs and the minimal set
of proteins required for RNA:Ψ-synthase activity is the aCBF5–aNOP10 protein pair. The crystal structure of the aCBF5–aNOP10
heterodimer from Pyrococcus abyssi was solved at 2.1 Å resolution. In this structure, protein aNOP10 ha...
A gapA-pgk gene tandem coding the glyceraldehyde 3-phosphate dehydrogenase and 3-phosphoglycerate kinase, is most frequently found in bacteria. However, in Enterobacteriaceae, gapA is replaced by an epd open reading frame (ORF) coding an erythrose-4-phosphate dehydrogenase and an fbaA ORF coding the class II fructose-1,6-bisphosphate aldolase follo...
Pseudouridine (Ψ) are frequently modified residues in RNA. In Eukarya, their formation is catalyzed by enzymes or by ribonucleoprotein
complexes (RNPs) containing H/ACA snoRNAs. H/ACA sRNA and putative ORFs for H/ACA sRNP proteins (L7Ae, aCBF5, aNOP10 and aGAR1)
were found in Archaea. Here, by using Pyrococcus abyssi recombinant proteins and an in...
The Escherichia coli multi-promoter region of the gapA gene ensures a high level of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) production under various growth conditions. In the exponential phase of growth, gapA mRNAs are mainly initiated at the highly efficient gapA P1 promoter. In the present study, by using site-directed mutagenesis and ch...
The ribosomal L7Ae protein of archaea has the peculiarity to be a component of the C/D and H/ACA snRNPs, that guide rRNA post-transcriptional modifications. Its yeast (Snu13p) and human (15.5kDa protein) homologs are only found in C/D snoRNPs and the (U4/U6, U5) spliceosomal tri-snRNP. By using a large variety of RNAs, we compared the RNA-binding s...
The L7Ae sRNP core protein from Pyrococcus abyssii was crystallized using the sitting-drop vapour-diffusion method. Crystals were obtained in the presence of MgCl(2), PEG 2000 MME and acetate buffer at pH 4.0. A native data set has been collected at 2.9 A resolution using a rotating-anode generator at room temperature. Crystals belong to the orthor...
The 15.5-kD protein and its yeast homolog Snu13p bind U4 snRNA, U3 snoRNA, and the C/D box snoRNAs. In U4 snRNA, they associate with a helix-bulge-helix (K-turn) structure. U3 snoRNA contains two conserved pairs of boxes, C′/D and B/C, which were both expected to bind the 15.5-kD/Snu13 protein. Only binding to the B/C motif was experimentally demon...
The bulge-helix-bulge (BHB) motif recognised by the archaeal splicing endonuclease is also found in the long processing stems of archaeal rRNA precursors in which it is cleaved to generate pre-16S and pre-23S rRNAs. We show that in two species, Archaeoglobus fulgidus and Sulfolobus solfataricus, representatives from the two major archaeal kingdoms...
The rubredoxin expression level in Clostridium butyricum DSM 5431 grown in continuous culture was monitored using primer extension analyses of the rub gene and a specific enzymatic assay of the iron-sulfur protein. In this way, we showed that variations in rubredoxin content and in rub mRNA level were influenced by the pH of the culture and were di...
The box C/D snoRNAs function in directing 2'-O-methylation and/or as chaperones in the processing of ribosomal RNA. We show here that Snu13p (15.5 kD in human), a component of the U4/U6.U5 tri-snRNP, is also associated with the box C/D snoRNAs. Indeed, genetic depletion of Snu13p in yeast leads to a major defect in RNA metabolism. The box C/D motif...
Using inverse PCR technique, a 831-bp DNA fragment containing the rubredoxin gene from Clostridium butyricum DSM 5431 was obtained. Sequencing of this fragment allowed us to deduce a 53-amino acid protein (molecular mass 5853 Da) with strong homology with other sequenced rubredoxins. Comparison of the sequences showed that the C. butyricum rubredox...
The Escherichia coli gapB gene codes for a protein that is very similar to bacterial glyceraldehyde-3-phosphate dehydrogenases (GAPDH). In most bacteria, the gene for GAPDH is located upstream of the pgk gene encoding 3-phosphoglycerate kinase (PGK). This is the case for gapB. However, this gene is poorly expressed and encodes a protein with an ery...
The export of pre-mRNAs coding for the structural genes of the human immunodeficiency virus type I depends on the interaction of the Rev protein with a highly structured viral RNA sequence, the Rev-responsive element (RRE). To gain information about the structure of the RRE and the determinants of the in vivo RRE-Rev interaction, we have analyzed t...
The nucleocapsid protein (NC) of HIV-1 is a small zinc finger protein that contributes to multiple steps of the viral life
cycle, including the proper encapsidation of HIV RNA. This is accomplished through an interaction between NC and a region
at the 5′-end of the RNA, defined as the Psi element. However, the specificity of NC for Psi or for RNA i...
rp5l B pre-mRNA, like many Saccharomyces cerevisiae primary transcripts, contains a secondary structure within its intron sequence. The structure is required for optimal in vivo splicing efficiency and includes two complementary regions near the 5' splice site and the branchpoint (UB1 and DB1, respectively). An intron-containing RNA was probed in v...
Escherichia coli D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is produced by the gapA gene and is structurally related to eukaryotic GAPDHs. These facts led to the proposal that the gapA gene originated by a horizontal transfer of genetic information. The yields and start sites of gapA mRNAs produced in various fermentation conditions and gen...
Escherichia coli D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is produced by the gapA gene and is structurally related to eukaryotic GAPDHs. These facts led to the proposal that the gapA gene originated by a horizontal transfer of genetic information. The yields and start sites of gapA mRNAs produced in various fermentation conditions and gen...
Citations
... Germ cells in female embryos undergo arrest during prophase 1 and remain in a state of inactivity until the moment of birth. Following the process of birth, oocytes undergo a series of developmental stages, including the primary follicle stage and the secondary follicle stage [15]. Methylation at germline differentially methylated regions (gDMRs) is created during this developmental phase, and it plays a crucial role in the formation and function of oocytes. ...
... The coding sequence for His 6 -DKC1(1-514)-AviTag was synthesized and cloned into pRSF-Duet TM -1 in MCS 2, replacing the His 6 -TEV-CypD(43-207)-AviTag coding sequence, by GenScript. The coding sequences for His 6 -RuvBL1(1-456)/RuvBL2(1-463), His 6 -RuvBL1_D302N/RuvBL2_D299N, and His 6 -RuvBL1_∆DII/RuvBL2_∆DII were synthesized and cloned as described in [22]. ...
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... En effet, TRBP et PACT, malgré leur similarité de séquence, conduisent à des spécificités différentes de clivage des ARN double-brin substrats par Dicer, ce qui peut produire des miARN matures de taille variable [4,5]. TRBP, en plus de son rôle au cours de la biogenèse des miARN, est impliquée dans la réplication du virus de RPAP3/PIH1D1), impliqué dans l'assemblage de différentes particules ribonucléoprotéiques, notamment les snoRNP, interagit avec TRBP [10]. Il a été montré que RPAP3 s'associait avec TRBP aussi efficacement que TRBP avec Dicer, mais qu'elle n'interagissait pas avec PACT, l'autre cofacteur de Dicer, pourtant paralogue de TRBP. ...
... Snord116 is likely critical in the pathogenesis of PWS given that microdeletion of the Snord116 cluster has been observed in a patient with PWS (Duker et al. 2010). Although multiple mRNA targets for Snord116 have been proposed based on sequence complementarity and evolutionary conservation, these putative targets have not been experimentally validated, and the mechanism by which Snord116 may contribute to PWS remains unclear (Baldini et al. 2022). Another neurodevelopmental disorder, non-syndrome X-linked intellectual disability (NSXLID), can be caused by mutations in FTSJ1, the 2′-O-methyltransferase that deposits Nm in the anticodon loop of certain tRNAs (Dimitrova et al. 2019). ...
... Nm and ψ are directed to rRNA sites by C/D snoRNP-and H/ACA snoRNP complexes, respectively. In these complexes sequence targeting is facilitated by distinct sets of snoRNAs [49,50] (Fig. 2). Three out of four proteins in the C/D snoRNP were quantified in our dataset and two were significantly upregulated (NOP56; 2.1-fold, p = 9.1E-5, NOP58; 2.1-fold, p = 3.8E-5). ...
... According to snoRNA structures, snoRNAs are mainly divided into two categories: C/D box snoRNAs and H/ACA box snoRNAs (Maxwell and Fournier 1995;Balakin et al. 1996;Kiss 2002). SnoRNAs are associated with specific proteins to form small nucleolar ribonucleoprotein (snoRNP) complexes, which participate in various biological processes (Watkins et al. 2004;Krastev et al. 2011;Bragantini et al. 2021;Wang et al. 2021b). With the development of computer technology and experimental approaches, more and more snoRNAs are identified and their functions revealed, such as gene expression, RNA synthesis, transport, and nucleotide modifications, etc. (Lowe and Eddy 1999;Huttenhofer et al. 2001;Zhao et al. 2017;Dong et al. 2020;Hasler et al. 2020Hasler et al. , 2021Yang et al. 2020;Deryusheva et al. 2021;Shi et al. 2021;Trucks et al. 2021). ...
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... For instance, the "superpathway of UDP-N-acetylglucosamine-derived O-antigen building blocks biosynthesis" exhibited associations with promoter methylation patterns across multiple genes, including C12orf45, GJD4, PNPLA8, MIR548X2, and LINC00380. Of significant interest, C12orf45 serves as a PAQosome cofactor, pivotal in facilitating the assembly of box C/D snoRNP [58]-an event observed to be elevated across various cancer types [59]. Equally noteworthy, the "coenzyme B biosynthesis" pathway demonstrated a positive correlation with NT5E promoter methylation. ...
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... In mammals, R2TP is composed of a heterodimer between PIH1D1 and RPAP3, which associates with a heterohexamer of RUVBL1 and RUVBL2 (Fig. 1a). PIH1D1 and RPAP3 are both involved in substrate recognition 4,5 while RPAP3 also recruits the chaperones HSP90 and HSP70 6,7 . RUVBL1 and RUVBL2 are related AAA+ ATPases that also have chaperone activity 8,9 . ...
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... While attempts to identify canonical K-turns within IAV genomes were not forthcoming, numerous studies have proposed that unique pseudoknots form during the splicing of segments 7 and 8 which then enable the assembly of a unique spliceosome (39)(40)(41). It should also be noted that there is no sequence conservation or little structural requirements to accurately predict K-turn formation (19,20,43). For this reason, it has been difficult to identify the exact location of the presumed hairpin and it remains possible that different strains deviate in sequence while maintaining an L7Ae substrate (19, 20, 43). ...
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... The formation of RNP complexes by RBPs generally requires the correct folding of the newly synthesized polypeptide chains into native configurations that can bind the RNA molecules, and involves protein phosphorylation, RNA-methylation, and other intricate processes (Li et al., 2011;Roh et al., 2016;Paul et al., 2019). In many or most cases, these processes require chaperonins to stabilize folding intermediates, maintain protein homeostasis and folded protein structures, and to mediate in transmembrane and intercellular transport (Horwich et al., 2007). ...
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