The Hsp90 chaperone controls the biogenesis of L7Ae RNPs through conserved machinery
Séverine BoulonNathalie Marmier‐GourrierBérengère Pradet‐BaladeLaurence WurthCéline VerheggenBeáta E. JádyBenjamin RothéChristina Begon-PesciaMarie-Cécile RobertTamás KissBarbara BardoniAlain KrolChristiane BranlantChristine AllmangÉdouard BertrandBruno Charpentier
219
Citation
37
Reference
10
Related Paper
Citation Trend
Abstract:
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 these RNPs. We observed that Rsa1 and Nufip bind several L7Ae proteins and tether them to other core proteins in the immature particles. Surprisingly, Rsa1 and Nufip also link assembling RNPs with the AAA + adenosine triphosphatases hRvb1 and hRvb2 and with the Hsp90 chaperone through two conserved adaptors, Tah1/hSpagh and Pih1. Inhibition of Hsp90 in human cells prevents the accumulation of U3, U4, and telomerase RNAs and decreases the levels of newly synthesized hNop58, hNHP2, 15.5K, and SBP2. Thus, Hsp90 may control the folding of these proteins during the formation of new RNPs. This suggests that Hsp90 functions as a master regulator of cell proliferation by allowing simultaneous control of cell signaling and cell growth.Keywords:
Small nucleolar RNA
Chaperone (clinical)
Non-coding RNAs (ncRNAs) are broadly classified as house-keeping and regulatory ncRNAs. The house keeping ncRNAs include the ribosomal RNA, transfer RNA, small nuclear RNA and snoRNA. While the regulatory ncRNA classification is based on length and include shorter microRNAs, snRNAs, piRNAs or the long ncRNAs (lncRNAs) that are greater than 200 nucleotides (nt) (1).
Small nucleolar RNA
Circular RNA
Cite
Citations (7)
Small nucleolar RNA
Ribonucleoprotein particle
Cite
Citations (57)
Small nucleolar RNA
Small nuclear ribonucleoprotein
Cite
Citations (238)
The isomerization of up to 100 uridines to pseudouridines (Ψs) in eukaryotic rRNA is guided by a similar number of box H/ACA small nucleolar RNAs (snoRNAs), each forming a unique small nucleolar ribonucleoprotein particle (snoRNP) with the same four core proteins, NAP57 (also known as dyskerin or Cbf5p), GAR1, NHP2, and NOP10. Additionally, the nucleolar and Cajal body protein Nopp140 (Srp40p) associates with the snoRNPs. To understand the role of these factors in pseudouridylation, we established an in vitro assay system. Short site-specifically 32P-labeled rRNA substrates were incubated with subcellular fractions, and the conversion of uridine to Ψ was monitored by thin-layer chromatography after digestion to single nucleotides. Immunopurified box H/ACA core particles were sufficient for the reaction. SnoRNPs associated quantitatively and reversibly with Nopp140. However, pseudouridylation activity was independent of Nopp140, consistent with a chaperoning role for this highly phosphorylated protein. Although up to 14 bp between the snoRNA and rRNA were required for the in vitro reaction, rRNA pseudouridylation and release occurred in the absence of ATP and magnesium. These data suggest that substrate release takes place without RNA helicase activity but may be aided by the snoRNP core proteins.
Small nucleolar RNA
Pseudouridine
Ribonucleoprotein particle
Cite
Citations (74)
Small nucleolar RNA
Cajal body
Small nuclear RNA
Heterogeneous ribonucleoprotein particle
Small nuclear ribonucleoprotein
snRNP
Cite
Citations (395)
Small nucleolar RNA
Cite
Citations (97)
Abstract About 85% of the human genome is transcribed into RNA. RNAs play essential roles in numerous cellular processes. Less than 2% of all transcripts are coding RNAs (messenger RNA). The remaining vast majority of RNAs do not encode protein and are collectively referred as noncoding RNA (ncRNA). Based on their biological functions, ncRNAs can be grouped into two categories: infrastructural and regulatory ncRNAs. Infrastructural ncRNAs mainly include ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs) and telomerase RNAs. The best‐characterised regulatory ncRNAs are microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Other regulatory ncRNAs include small inhibitory RNAs (siRNAs), Piwi‐interacting RNAs (piRNAs) and circular RNAs (circRNA). This article will summarise the structure and function of major RNA categories. Three RNA types are essential for protein synthesis: mRNA carries genetic code; tRNA transfers protein codon; and rRNA makes up the ribosomes in which translation takes place. About 85% of the human genome is transcribed into RNA. Only <2% of RNAs are coding RNAs (mRNAs) and the remaining RNAs are noncoding RNAs (ncRNAs). Noncoding RNAs can be grouped into two categories: infrastructural and regulatory ncRNAs. Infrastructural ncRNAs mainly include rRNAs, tRNAs, snRNAs, and snoRNAs. The major regulatory ncRNAs include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). SnRNAs are often rich in uridylic acid and a group of U‐snRNAs and associated proteins form spliceosome and are responsible for pre‐mRNA splicing. SnoRNAs can be classified into two large subfamilies: C/D‐box (SNORA) and H/ACA‐box (SNORD). The main functions of snoRNAs are in the processing and maturation of pre‐rRNAs and posttranscriptional modification (methylation and pseudouridylation) of rRNA. Three small ncRNAs, siRNA, miRNA and piRNA, form RNA‐induced silencing complex (RISC) to exert posttranscriptional gene regulation by binding to 3′ UTR of target mRNAs and either inducing mRNA degradation (perfect match) or impeding translation (imperfect match). miRNAs are the major type of small ncRNAs. The biogenesis of miRNAs is a multistep process, from long primary miRNA transcripts (pri‐miRNAs) to pre‐miRNAs of ∼70 nucleotides long and to mature miRNA of ∼22 nucleotides. piRNAs mainly function in the germ line of animals to silence transposons and other repetitive elements and maintain genomic stability. lncRNAs are >200 nucleotides long. There are thousands of lncRNAs and the majority have not been functionally characterised. But many have been shown to posttranscriptionally regulate gene expression through various mechanisms. Unlike the better‐known linear RNA, circRNAs is a type of single‐stranded RNA that are covalently closed with no 5′ end caps or 3′ poly(A) tails. Some circRNAs can serve as miRNA and protein sponges to sequester miRNA/protein and regulate gene expression.
Small nucleolar RNA
Small nuclear RNA
Piwi-interacting RNA
Cite
Citations (0)
积累的证据建议非编码的 RNA (ncRNAs ) 在许多真核细胞的有机体普遍、机能上地重要。在这研究，我们采用了分别和 cDNA 图书馆构造方法列在后面由的一种特殊尺寸 454 系统地介绍米饭的深定序中间尺寸的 ncRNAs。我们的分析总共导致了 1349 ncRNAs 的鉴定，包括一个未知功能的范畴的 754 新奇 ncRNAs。所有识别 ncRNAs 的染色体分发没显示出海滨偏爱，并且显示了类似于与很少染色体相关性在编码蛋白质的基因观察了那的一个模式。非常， ncRNAs 的一半被集中在附近编码区域的 5 和 3 个终点正海滨。新奇 ncRNAs 的多数是米饭特定，当 78% 小核仁的 RNA (snoRNAs ) 被保存时。双人脚踏车复制驾驶了扩大在 snoRNA 基因家庭的一半上。而且， 90% snoRNA 候选人被显示特别地生产在 2030 nt，其 80% 通常与淘金者蛋白质被联系，和 AGO1b 之间的小 RNA。总的来说，我们的调查结果在 monocot 种提供中间尺寸的非编码的 transcriptome 的一个全面看法，它将为 ncRNA 函数的深入的分析用作一个有用平台。
Small nucleolar RNA
RNA Silencing
Cite
Citations (0)
Eukaryotes and archaea use two sets of specialized ribonucleoproteins (RNPs) to carry out sequence-specific methylation and pseudouridylation of RNA, the two most abundant types of modifications of cellular RNAs. In eukaryotes, these protein–RNA complexes localize to the nucleolus and are called small nucleolar RNPs (snoRNPs), while in archaea they are known as small RNPs (sRNP). The C/D class of sno(s)RNPs carries out ribose-2′-O-methylation, while the H/ACA class is responsible for pseudouridylation of their RNA targets. Here, we review the recent advances in the structure, assembly and function of the conserved C/D and H/ACA sno(s)RNPs. Structures of each of the core archaeal sRNP proteins have been determined and their assembly pathways delineated. Furthermore, the recent structure of an H/ACA complex has revealed the organization of a complete sRNP. Combined with current biochemical data, these structures offer insight into the highly homologous eukaryotic snoRNPs.
Small nucleolar RNA
Nucleic acid structure
Cite
Citations (361)
Ribonucleic acids (RNAs) are very complex and their all functions have yet to be fully clarified. Noncoding genes (noncoding RNA, sequences, and pseudogenes) comprise 67% of all genes and they are represented by housekeeping noncoding RNAs (transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), and small nucleolar RNA (snoRNA)) that are engaged in basic cellular processes and by regulatory noncoding RNA (short and long noncoding RNA (ncRNA)) that are important for gene expression/transcript stability. In this review, we summarize data concerning the significance of long noncoding RNAs (lncRNAs) in metabolic syndrome related disorders, focusing on adipose tissue and pancreatic islands.
Small nucleolar RNA
Pseudogene
Small nuclear RNA
Cite
Citations (70)