Widespread intron retention in mammals functionally tunes transcriptomes
By Ulrich Braunschweig, Nuno L. Barbosa-Morais, Qun Pan, Emil N. Nachman, Babak Alipanahi, Thomas Gonatopoulos-Pournatzis, Brendan J. Frey, Manuel Irimia, Benjamin J. Blencowe. Genome Research, 2014
630 citations recorded by the source corpus.
Alternative splicing (AS) of precursor RNAs is responsible for greatly expanding the regulatory and functional capacity of eukaryotic genomes. Of the different classes of AS, intron retention (IR) is the least well understood. In plants and unicellular eukaryotes, IR is the most common form of AS, whereas in animals, it is thought to represent the least prevalent form. Using high-coverage poly(A)+ RNA-seq data, we observe that IR is surprisingly frequent in mammals, affecting transcripts from as many as three-quarters of multiexonic genes. A highly correlated set of cis features comprising an “IR code” reliably discriminates retained from constitutively spliced introns. We show that IR acts widely to reduce the levels of transcripts that are less or not required for the physiology of the cell or tissue type in which they are detected. This “transcriptome tuning” function of IR acts through both nonsense-mediated mRNA decay and nuclear sequestration and turnover of IR transcripts. We further show that IR is linked to a cross-talk mechanism involving localized stalling of RNA polymerase II (Pol II) and reduced availability of spliceosomal components. Collectively, the results implicate a global checkpoint-type mechanism whereby reduced recruitment of splicing components coupled to Pol II pausing underlies widespread IR-mediated suppression of inappropriately expressed transcripts.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f964f3ef4763a3a501da5d867551af97edadf3be
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In Molecular Biology
- Neelroop Parikshak
- Thomas Gonatopoulos-Pournatzis
- Michael J.E. Sternberg
- Manuel Irimia
- Frederick P. Roth
- Jeffrey L. Wrana
- Benjamin J. Blencowe
- Daniel H. Geschwind
Citations in the corpus
- Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome (2017, background): “…has shown that intron retention might be a conserved and more common mode of transcript regulation than previously appreciated (Galante et al. 2004; Braunschweig et al. 2014; Boutz et al. 2015; Mudvari et al. 2015; Wong et al. 2016), with examples found in hematopoiesis (Wong et al. 2013; Edwards…”
- A highly conserved program of neuronal microexons is misregulated in autistic brains (2014, methodology): “However, the function of the vast majority of AS events detected to date are not known, and new landscapes of AS regulation remain to be discovered and characterized (Braunschweig et al., 2014; Eom et al., 2013).”