Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression

Lianoglou, Steve; Garg, Vidur; Yang, Julie; Leslie, Christina; Mayr, Christine

doi:10.1101/gad.229328.113

Cited by 365 publications

(545 citation statements)

References 62 publications

(95 reference statements)

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“…Therefore, based on such analysis of a number of data sets, we have corrected the K values for a few RP mRNAs (Supplemental Table S4). A recent analysis of polyadenylation sites largely confirms these corrections and provides interesting examples of tissue-specific differences in 3 ′ termination sites for some RP transcripts (Lianoglou et al 2013).…”

Section: Genes Encoding Ribosomal Proteins and Their Derivativesmentioning

confidence: 74%

Ribosome-omics of the human ribosome

Gupta

Warner

2014

RNA

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The torrent of RNA-seq data becoming available not only furnishes an overview of the entire transcriptome but also provides tools to focus on specific areas of interest. Our focus on the synthesis of ribosomes asked whether the abundance of mRNAs encoding ribosomal proteins (RPs) matched the equimolar need for the RPs in the assembly of ribosomes. We were at first surprised to find, in the mapping data of ENCODE and other sources, that there were nearly 100-fold differences in the level of the mRNAs encoding the different RPs. However, after correcting for the mapping ambiguities introduced by the presence of more than 2000 pseudogenes derived from RP mRNAs, we show that for 80%-90% of the RP genes, the molar ratio of mRNAs varies less than threefold, with little tissue specificity. Nevertheless, since the RPs are needed in equimolar amounts, there must be sluggish or regulated translation of the more abundant RP mRNAs and/or substantial turnover of unused RPs. In addition, seven of the RPs have subsidiary genes, three of which are pseudogenes that have been "rescued" by the introduction of promoters and/or upstream introns. Several of these are transcribed in a tissue-specific manner, e.g., RPL10L in testis and RPL3L in muscle, leading to potential variation in ribosome structure from one tissue to another. Of the 376 introns in the RP genes, a single one is alternatively spliced in a tissue-specific manner.

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Section: Genes Encoding Ribosomal Proteins and Their Derivativesmentioning

confidence: 74%

Ribosome-omics of the human ribosome

Gupta

Warner

2014

RNA

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“…Several 3 ′ -end sequencing data sets have recently been published that include different mammalian tissues with variable coverage and depths (Derti et al 2012;Lin et al 2012;Lianoglou et al 2013). For our initial modeling, we chose to use the data set generated by the Mayr laboratory that covers seven human tissues, including naive B cells, brain, breast, embryonic stem (ES) cells, ovary, skeletal muscle, and testis (Lianoglou et al 2013). We used the "cleaned alignment" version of their 3 ′ seq data set, in which only uniquely mapped reads were kept and internal priming or spurious antisense reads were computationally removed.…”

Section: Mrnamentioning

confidence: 99%

Poly(A) code analyses reveal key determinants for tissue-specific mRNA alternative polyadenylation

Weng

Xie

et al. 2016

RNA

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mRNA alternative polyadenylation (APA) is a critical mechanism for post-transcriptional gene regulation and is often regulated in a tissue-and/or developmental stage-specific manner. An ultimate goal for the APA field has been to be able to computationally predict APA profiles under different physiological or pathological conditions. As a first step toward this goal, we have assembled a poly(A) code for predicting tissue-specific poly(A) sites (PASs). Based on a compendium of over 600 features that have known or potential roles in PAS selection, we have generated and refined a machine-learning algorithm using multiple high-throughput sequencing-based data sets of tissue-specific and constitutive PASs. This code can predict tissue-specific PASs with >85% accuracy. Importantly, by analyzing the prediction performance based on different RNA features, we found that PAS context, including the distance between alternative PASs and the relative position of a PAS within the gene, is a key feature for determining the susceptibility of a PAS to tissue-specific regulation. Our poly(A) code provides a useful tool for not only predicting tissue-specific APA regulation, but also for studying its underlying molecular mechanisms.

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“…As a result the first nucleotides identified are located internal to the 3 ′ end of the molecule. A number of methods for locating alternative polyadenylation sites have been developed (Mayr and Bartel 2009;Shepard et al 2011;Lianoglou et al 2013;Hoque et al 2014;Masamha et al 2014), only some of which rely on sequencing the junction between the nontemplated poly(A) tail and the cleavage site to identify the precise nucleotide where poly(A) is added (Martin et al 2012;Hoque et al 2014;Yao and Shi 2014).…”

Section: Introductionmentioning

confidence: 99%

EnD-Seq and AppEnD: sequencing 3′ ends to identify nontemplated tails and degradation intermediates

Welch

Slevin

Tatomer³

et al. 2015

RNA

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Existing methods for detecting RNA intermediates resulting from exonuclease degradation are low-throughput and laborious. In addition, mapping the 3 ′ ends of RNA molecules to the genome after high-throughput sequencing is challenging, particularly if the 3 ′ ends contain post-transcriptional modifications. To address these problems, we developed EnD-Seq, a high-throughput sequencing protocol that preserves the 3 ′ end of RNA molecules, and AppEnD, a computational method for analyzing highthroughput sequencing data. Together these allow determination of the 3 ′ ends of RNA molecules, including nontemplated additions. Applying EnD-Seq and AppEnD to histone mRNAs revealed that a significant fraction of cytoplasmic histone mRNAs end in one or two uridines, which have replaced the 1-2 nt at the 3 ′ end of mature histone mRNA maintaining the length of the histone transcripts. Histone mRNAs in fly embryos and ovaries show the same pattern, but with different tail nucleotide compositions. We increase the sensitivity of EnD-Seq by using cDNA priming to specifically enrich low-abundance tails of known sequence composition allowing identification of degradation intermediates. In addition, we show the broad applicability of our computational approach by using AppEnD to gain insight into 3 ′ additions from diverse types of sequencing data, including data from small capped RNA sequencing and some alternative polyadenylation protocols.

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Ubiquitously transcribed genes use alternative polyadenylation to achieve tissue-specific expression

Cited by 365 publications

References 62 publications

Ribosome-omics of the human ribosome

Ribosome-omics of the human ribosome

Poly(A) code analyses reveal key determinants for tissue-specific mRNA alternative polyadenylation

EnD-Seq and AppEnD: sequencing 3′ ends to identify nontemplated tails and degradation intermediates

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