We describe the crystal structure of the complete Thermus thermophilus 70S ribosome containing bound messenger RNA and transfer RNAs (tRNAs) at 5.5 angstrom resolution. All of the 16S, 23S, and 5S ribosomal RNA (rRNA) chains, the A-, P-, and E-site tRNAs, and most of the ribosomal proteins can be fitted to the electron density map. The core of the interface between the 30S small subunit and the 50S large subunit, where the tRNA substrates are bound, is dominated by RNA, with proteins located mainly at the periphery, consistent with ribosomal function being based on rRNA. In each of the three tRNA binding sites, the ribosome contacts all of the major elements of tRNA, providing an explanation for the conservation of tRNA structure. The tRNAs are closely juxtaposed with the intersubunit bridges, in a way that suggests coupling of the 20 to 50 angstrom movements associated with tRNA translocation with intersubunit movement.

https://science.sciencemag.org/content/sci/292/5518/883.full.pdf

Crystal structure of the ribosome at 5.5 A resolution

https://www.hal.inserm.fr/inserm-02452742/document

Biogenesis and secretion of exosomes

Short interfering RNAs (siRNAs) are double-stranded RNAs of ’21‐25 nucleotides that have been shown to function as key intermediaries in triggering sequence-specific RNA degradation during posttranscriptional gene silencing in plants and RNA interference in invertebrates siRNAs have a characteristic structure, with 5*-phosphatey3*-hydroxyl ends and a 2-base 3* overhang on each strand of the duplex In this study, we present data that synthetic siRNAs can induce gene-specific inhibition of expression in Caenorhabditis elegans and in cell lines from humans and mice In each case, the interference by siRNAs was superior to the inhibition of gene expression mediated by single-stranded antisense oligonucleotides The siRNAs seem to avoid the well documented nonspecific effects triggered by longer double-stranded RNAs in mammalian cells These observations may open a path toward the use of siRNAs as a reverse genetic and therapeutic tool in mammalian cells

/pdf/specific-inhibition-of-gene-expression-by-small-double-4ot4xfxzyk.pdf

Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems.

Turnover of mRNA is a key mechanism in regulated gene expression. In addition to turnover pathways for normal transcripts, there are surveillance mechanisms that degrade aberrant mRNAs. mRNA decay is regulated in response to cellular signals and coordinated with other mRNA-metabolic processes. When considering the control of gene expression, the focus has traditionally been on transcriptional regulation. Recently, however, the large contribution made by mRNA decay has become difficult to ignore. Large-scale analyses indicate that as many as half of all changes in the amounts of mRNA in some responses can be attributed to altered rates of decay. In this article, we discuss some of the mechanisms that are used by the cell to mediate and regulate this intriguing process.

The highways and byways of mRNA decay.

Nonsense-mediated mRNA decay (NMD) is a quality-control mechanism that selectively degrades mRNAs harboring premature termination (nonsense) codons. If translated, these mRNAs can produce truncated proteins with dominant-negative or deleterious gain-of-function activities. In this review, we describe the molecular mechanism of NMD. We first cover conserved factors known to be involved in NMD in all eukaryotes. We then describe a unique protein complex that is deposited on mammalian mRNAs during splicing, which defines a stop codon as premature. Interaction between this exon-junction complex (EJC) and NMD factors assembled at the upstream stop codon triggers a series of steps that ultimately lead to mRNA decay. We discuss whether these proofreading events preferentially occur during a “pioneer” round of translation in higher and lower eukaryotes, their cellular location, and whether they can use alternative EJC factors or act independent of the EJC.

/pdf/the-nonsense-mediated-decay-rna-surveillance-pathway-574xg7wv5x.pdf

The Nonsense-Mediated Decay RNA Surveillance Pathway

The Exosome: A Conserved Eukaryotic RNA Processing Complex Containing Multiple 3′→5′ Exoribonucleases

We previously identified a complex of 3' --> 5' exoribonucleases, designated the exosome, that is expected to play a major role in diverse RNA processing and degradation pathways. Further biochemical and genetic analyses have revealed six novel components of the complex. Therefore, the complex contains 11 components, 10 of which are predicted to be 3' --> 5' exoribonucleases on the basis of sequence homology. Human homologs were identified for 9 of the 11 yeast exosome components, three of which complement mutations in the respective yeast genes. Two of the newly identified exosome components are homologous to known components of the PM-Scl particle, a multisubunit complex recognized by autoimmune sera of patients suffering from polymyositis-scleroderma overlap syndrome. We demonstrate that the homolog of the Rrp4p exosome subunit is also a component of the PM-Scl complex, thereby providing compelling evidence that the yeast exosome and human PM-Scl complexes are functionally equivalent. The two complexes are similar in size, and biochemical fractionation and indirect immunofluorescence experiments show that, in both yeast and humans, nuclear and cytoplasmic forms of the complex exist that differ only by the presence of the Rrp6p/PM-Scl100 subunit exclusively in the nuclear complex.

/pdf/the-yeast-exosome-and-human-pm-scl-are-related-complexes-of-2mzru3mdog.pdf

The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases.

Eukaryotic rRNAs (with the exception of 5S rRNA) are synthesized from a contiguous pre-rRNA precursor by a complex series of processing reactions. Final maturation of yeast 5.8S rRNA involves processing of a 3'-extended, 7S precursor that contains -140 nucleotides of the internal transcribed spacer 2 (ITS2) region. In yeast strains carrying the temperature-sensitive (ts) rrp4-1 mutation, 5.8S rRNA species were observed with 3' extensions of variable length extending up to the 3' end of the 7S pre-rRNA. These 3'-extended 5.8S rRNA species were observed at low levels in rrp4-1 strains under conditions permissive for growth and increased in abundance upon transfer to the nonpermissive temperature. The RRP4 gene was cloned by complementation of the ts growth phenotype of rrp4-1 strains. RRP4 encodes an essential protein of 39-kD predicted molecular mass. Immunoprecipitated Rrp4p exhibited a 3' --~ 5' exoribonuclease activity in vitro that required RNA with a 3'-terminal hydroxyl group and released nucleoside 5' monophosphates. We conclude that the 7S pre-rRNA is processed to 5.8S rRNA by a 3' --* 5' exonuclease activity involving Rrp4p. Homologs of Rrp4p are found in both humans and the fission yeast Schizosaccaromyces pombe (43% and 52% identity, respectively), suggesting that the mechanism of 5.8S rRNA 3' end formation has been conserved throughout eukaryotes.

/pdf/the-3-end-of-yeast-5-8s-rrna-is-generated-by-an-exonuclease-3eori0siib.pdf

The 3' end of yeast 5.8S rRNA is generated by an exonuclease processing mechanism.

Two forms of the yeast 5.8S rRNA are generated from a large precursor by distinct processing pathways. Cleavage at site A3 is required for synthesis of the major, short form, designated 5.8S(S), but not for synthesis of the long form, 5.8S(L). To identify components required for A3 cleavage, a bank of temperature-sensitive lethal mutants was screened for those with a reduced ratio of 5.8S(S):5.8S(L). The pop1-1 mutation (for processing of precursor RNAs) shows this phenotype and also inhibits A3 cleavage. The pre-rRNA processing defect of pop1-1 strains is similar to that reported for mutations in the RNA component of RNase MRP; we show that a mutation in the RNase MRP RNA also inhibits cleavage at site A3. This is the first site shown to require RNase MRP for cleavage in vivo. The pop1-1 mutation also leads to a block in the processing of pre-tRNA that is identical to that reported for mutations in the RNA component of RNase P. The RNA components of both RNase MRP and RNase P are underaccumulated in pop1-1 strains at the nonpermissive temperature, and immunoprecipitation demonstrates that POP1p is a component of both ribonucleoproteins. The POP1 gene encodes a protein with a predicted molecular mass of 100.5 kD and is essential for viability. POP1p is the first protein component of the nuclear RNase P or RNase MRP for which the gene has been cloned.

/pdf/the-pop1-gene-encodes-a-protein-component-common-to-the-3qeipw2p4u.pdf

The POP1 gene encodes a protein component common to the RNase MRP and RNase P ribonucleoproteins.

Short Article An NMD Pathway in Yeast Involving Accelerated Deadenylation and Exosome-Mediated 3! ! 5! Degradation

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Philip Mitchell

Author Tools

Chat about Author