http://www.cs.duke.edu/courses/cps262/current/pdf/hafner.2010.pdf

Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIP

Long non-coding RNAs (lncRNAs) are a diverse class of RNAs that engage in numerous biological processes across every branch of life. Although initially discovered as mRNA-like transcripts that do not encode proteins, recent studies have revealed features of lncRNAs that further distinguish them from mRNAs. In this Review, we describe special events in the lifetimes of lncRNAs - before, during and after transcription - and discuss how these events ultimately shape the unique characteristics and functional roles of lncRNAs.

Unique features of long non-coding RNA biogenesis and function

Circular Intronic Long Noncoding RNAs

Small RNA guides--microRNAs, small interfering RNAs, and repeat-associated small interfering RNAs, 21 to 30 nucleotides in length--shape diverse cellular pathways, from chromosome architecture to stem cell maintenance. Fifteen years after the discovery of RNA silencing, we are only just beginning to understand the depth and complexity of how these RNAs regulate gene expression and to consider their role in shaping the evolutionary history of higher eukaryotes.

/pdf/ribo-gnome-the-big-world-of-small-rnas-5gfal1tolg.pdf

Ribo-gnome: the big world of small RNAs

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.

https://www.cell.com/cell/pdf/S0092-8674(05)00442-3.pdf

RNA degradation by the exosome is promoted by a nuclear polyadenylation complex

The yeast nuclear exosome contains multiple 3′→5′ exoribonucleases, raising the question of why so many activities are present in the complex. All components are required during the 3′ processing of the 5.8S rRNA, together with the putative RNA helicase Dob1p/Mtr4p. During this processing three distinct steps can be resolved, and hand‐over between different exonucleases appears to occur at least twice. 3′ processing of snoRNAs (small nucleolar RNAs) that are excised from polycistronic precursors or from mRNA introns is also a multi‐step process that involves the exosome, with final trimming specifically dependent on the Rrp6p component. The spliceosomal U4 snRNA (small nuclear RNA) is synthesized from a 3′ extended precursor that is cleaved by Rnt1p at sites 135 and 169 nt downstream of the mature 3′ end. This cleavage is followed by 3′→5′ processing of the pre‐snRNA involving the exosome complex and Dob1p. The exosome, together with Rnt1p, also participates in the 3′ processing of the U1 and U5 snRNAs. We conclude that the exosome is involved in the processing of many RNA substrates and that different components can have distinct functions.

/pdf/functions-of-the-exosome-in-rrna-snorna-and-snrna-synthesis-tahdavrong.pdf

Functions of the exosome in rRNA, snoRNA and snRNA synthesis.

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.

90S Pre-Ribosomes Include the 35S Pre-rRNA, the U3 snoRNP, and 40S Subunit Processing Factors but Predominantly Lack 60S Synthesis Factors

60S ribosomes undergo initial assembly in the nucleolus before export to the cytoplasm and recent analyses have identified several nucleolar pre-60S particles. To unravel the steps in the pathway of ribosome formation, we have purified the pre-60S ribosomes associated with proteins predicted to act at different stages as the pre-ribosomes transit from the nucleolus through the nucleoplasm and are then exported to the cytoplasm for final maturation. About 50 non-ribosomal proteins are associated with the early nucleolar pre-60S ribosomes. During subsequent maturation and transport to the nucleoplasm, many of these factors are removed, while others remain attached and additional factors transiently associate. When the 60S precursor particles are close to exit from the nucleus they associate with at least two export factors, Nmd3 and Mtr2. As the 60S pre-ribosome reaches the cytoplasm, almost all of the factors are dissociated. These data provide an initial biochemical map of 60S ribosomal subunit formation on its path from the nucleolus to the cytoplasm.

/pdf/60s-pre-ribosome-formation-viewed-from-assembly-in-the-dsl3u96rko.pdf

Elisabeth Petfalski

Papers

RNA degradation by the exosome is promoted by a nuclear polyadenylation complex

Functions of the exosome in rRNA, snoRNA and snRNA synthesis.

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

90S Pre-Ribosomes Include the 35S Pre-rRNA, the U3 snoRNP, and 40S Subunit Processing Factors but Predominantly Lack 60S Synthesis Factors

60S pre‐ribosome formation viewed from assembly in the nucleolus until export to the cytoplasm