Poly(A)-tail profiling reveals an embryonic switch in translational control

Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measu...

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Bibliographic Details
Main Authors: Subtelny, Alexander Orest, Eichhorn, Stephen William, Chen, Grace, Sive, Hazel L., Bartel, David
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: Nature Publishing Group 2015
Online Access:http://hdl.handle.net/1721.1/96227
https://orcid.org/0000-0002-6410-4699
https://orcid.org/0000-0002-3872-2856
https://orcid.org/0000-0002-4890-424X
https://orcid.org/0000-0001-5029-5909
https://orcid.org/0000-0001-9051-1696
Description
Summary:Poly(A) tails enhance the stability and translation of most eukaryotic messenger RNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis thaliana leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other ‘housekeeping’ proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiencies in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.