Genome-wide Analysis of Pre-mRNA 3′ End Processing Reveals a Decisive Role of Human Cleavage Factor I in the Regulation of 3′ UTR Length

Martín, Georges; Gruber, Andreas; Keller, Walter; Zavolan, Mihaela

doi:10.1016/j.celrep.2012.05.003

Cited by 335 publications

(450 citation statements)

References 62 publications

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“…In all eukaryotic species studied, the overall PAS regions are A/U-rich with alternating U-and A-rich elements ( Fig. 2A; Jan et al 2010;Ozsolak et al 2010;Martin et al 2012;Sherstnev et al 2012;Ulitsky et al 2012). These include the U-rich USEs (>30 nt upstream of the cleavage site), an A-rich region (from À10 to À30 nt), and U-rich elements both upstream of and downstream from the cleavage sites.…”

Section: Insights From Global Studies Of Apamentioning

confidence: 99%

“…The most commonly used methods rely on oligo(dT)-primed reverse transcription-PCR (RT-PCR) for library construction (Mangone et al 2010;Fox-Walsh et al 2011;Fu et al 2011;Shepard et al 2011;Derti et al 2012). Different versions of this method have been described with modifications designed to improve library construction and/or to facilitate sequencing (Shepard et al 2011;Derti et al 2012;Martin et al 2012). The obvious advantage of the approach is its simplicity and quantitative nature.…”

Section: Technologies For Global Apa Analysesmentioning

confidence: 99%

“…To address these limitations, multiple computational approaches have been developed to filter out the majority of sequencing reads generated by internal priming (Mangone et al 2010;Derti et al 2012). Recent studies have demonstrated that these methods are highly effective in detecting global APA changes Shepard et al 2011;Jenal et al 2012;Martin et al 2012). A more sophisticated and laborintensive method, called 3P-seq, uses more enzymatic steps for library construction, but avoids oligo(dT) priming and the associated internal priming issue (Jan et al 2010).…”

Section: Technologies For Global Apa Analysesmentioning

confidence: 99%

“…Modifications of this method, such as PAR-CLIP (PhotoactivatableRibonucleoside-Enhanced CLIP) and iCLIP (individualnucleotide resolution CLIP), were subsequently introduced to improve the cross-linking efficiency and/or mapping resolution (Hafner et al 2010;Konig et al 2010). Recently, PAR-CLIP has been applied to globally mapping the RNAbinding sites for many core 39 processing factors (Martin et al 2012). Integration of transcriptome-wide protein-RNA interaction mapping with global functional analyses allows for construction of information-rich mechanistic models, called ''RNA maps'' (Licatalosi et al 2008;Yeo et al 2009).…”

Section: Technologies For Global Apa Analysesmentioning

confidence: 99%

“…These include the U-rich USEs (>30 nt upstream of the cleavage site), an A-rich region (from À10 to À30 nt), and U-rich elements both upstream of and downstream from the cleavage sites. For all metazoans and Arabidopsis, AAUAAA is the most common hexamer found in the A-rich regions and its close variants are also detected in a significant portion of PASs (Jan et al 2010;Ozsolak et al 2010;Martin et al 2012;Sherstnev et al 2012;Ulitsky et al 2012). Therefore, the nucleotide composition, key ciselements, and their spatial organization seem well conserved in metazoans and plant.…”

Section: Insights From Global Studies Of Apamentioning

confidence: 99%

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Alternative polyadenylation: New insights from global analyses

Shi

2012

RNA

196

187

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Recent studies have revealed widespread mRNA alternative polyadenylation (APA) in eukaryotes and its dynamic spatial and temporal regulation. APA not only generates proteomic and functional diversity, but also plays important roles in regulating gene expression. Global deregulation of APA has been demonstrated in a variety of human diseases. Recent exciting advances in the field have been made possible in a large part by high throughput analyses using newly developed experimental tools. Here I review the recent progress in global studies of APA and the insights that have emerged from these and other studies that use more conventional methods.

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Section: Insights From Global Studies Of Apamentioning

confidence: 99%

Section: Technologies For Global Apa Analysesmentioning

confidence: 99%

Section: Technologies For Global Apa Analysesmentioning

confidence: 99%

Section: Technologies For Global Apa Analysesmentioning

confidence: 99%

Section: Insights From Global Studies Of Apamentioning

confidence: 99%

See 3 more Smart Citations

Alternative polyadenylation: New insights from global analyses

Shi

2012

RNA

196

187

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The 3′ UTR Landscape in Cancer

Schmidt¹,

Ghosh²,

Zavolan³

2018

Encyclopedia of Life Sciences

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Oncogenesis is tightly connected with dysregulated gene expression. Alterations occur at many levels, including in posttranscriptional regulatory elements that control the stability, cellular localisation or translation efficiency of messenger ribonucleic acids (mRNAs). These elements are located primarily in the 3′ untranslated region (UTR) of mRNAs. Multiple examples are known of oncogenes whose activity and function become altered owing to changes in their 3′ UTRs. Strikingly, recent studies have uncovered global changes of 3′ UTRs in cancers, going beyond individual genes. Cancer cells express transcripts with systematically shorter 3′ UTRs compared to normal cells. The implications of these changes for cellular biology are poorly understood, but high‐throughput approaches are being developed to uncover the regulators, targets and impact of 3′ UTR‐based regulation. The hope is that a renewed understanding of 3′ UTR alterations can open new therapeutic opportunities. Key Concepts The maturation of most messenger RNAs includes 3′ end cleavage followed by the addition of a polyadenosine tail. Most human protein‐coding genes express multiple isoforms, which can differ, among others, in their 3′ untranslated regions (3′ UTRs). In proliferating cells, including cancer cells, cleavage and polyadenylation tend to occur at coding region proximal sites, giving rise to isoforms with short 3′ UTRs. As 3′ UTRs contain binding sites for many RNA‐binding regulatory proteins, it is likely that short 3′ UTR isoforms are less susceptible to posttranscriptional regulation. A role of 3′ UTR length changes in the progression and prognosis of cancers has been proposed.

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mRNA Formation: 3′‐End

Wahle

Kühn

2021

Encyclopedia of Life Sciences

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Eukaryotic mRNAs are derived from precursors synthesised by RNA polymerase II. For 3′‐end formation, precursors are cleaved by an endonuclease, and a poly(A) tail is added. This processing reaction depends on signals in the pre‐mRNA, among them the ‘polyadenylation signal’ AAUAAA. Cleavage and polyadenylation are carried out by a multiprotein complex comprising, in yeast, a minimum of 13 polypeptides, many of which recognise RNA sequence motifs around the polyadenylation site. 3′‐end processing is coupled to transcription. Alternative polyadenylation, that is cleavage and polyadenylation of a precursor RNA at any of several sites, is widespread. The choice of polyadenylation site can affect the coding sequence or, more often, 3′‐UTR length. In the latter case, stability, translational efficiency or localisation of the RNA may be affected. Histone mRNAs are an exception: Their precursors are cleaved by a partially different set of factors, and no poly(A) tail is added. Key Concepts The 3′‐ends of eukaryotic mRNAs are generated by processing of the primary transcript, not by transcription termination. 3′‐end processing is essential for the production of mRNAs. 3′‐end processing takes place in the cell nucleus and consists of cleavage of the primary transcript followed by addition of a poly(A) tail to the upstream cleavage product. The machinery for 3′‐end processing is complex, comprising at least 13 polypeptides. 3′‐end processing occurs cotranscriptionally and is coupled to transcription and splicing. Alternative polyadenylation, that is the choice of different sites for cleavage and polyadenylation, can change the protein sequence encoded by the resulting mRNAs and/or mRNA regulation. Histone mRNAs in metazoans are the only known RNAs that are not polyadenylated; their 3′‐ends are generated by a simple cleavage reaction.

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Genome-wide Analysis of Pre-mRNA 3′ End Processing Reveals a Decisive Role of Human Cleavage Factor I in the Regulation of 3′ UTR Length

Cited by 335 publications

References 62 publications

Alternative polyadenylation: New insights from global analyses

Alternative polyadenylation: New insights from global analyses

The 3′ UTR Landscape in Cancer

mRNA Formation: 3′‐End

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