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Mol Cell. 2017 Jul 6;67(1):71-83.e7. doi: 10.1016/j.molcel.2017.05.021. Epub 2017 Jun 15.

Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide.

Author information

1
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
2
Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
3
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
4
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
5
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: mbarna@stanford.edu.

Abstract

Emerging studies have linked the ribosome to more selective control of gene regulation. However, an outstanding question is whether ribosome heterogeneity at the level of core ribosomal proteins (RPs) exists and enables ribosomes to preferentially translate specific mRNAs genome-wide. Here, we measured the absolute abundance of RPs in translating ribosomes and profiled transcripts that are enriched or depleted from select subsets of ribosomes within embryonic stem cells. We find that heterogeneity in RP composition endows ribosomes with differential selectivity for translating subpools of transcripts, including those controlling metabolism, cell cycle, and development. As an example, mRNAs enriched in binding to RPL10A/uL1-containing ribosomes are shown to require RPL10A/uL1 for their efficient translation. Within several of these transcripts, this level of regulation is mediated, at least in part, by internal ribosome entry sites. Together, these results reveal a critical functional link between ribosome heterogeneity and the post-transcriptional circuitry of gene expression.

KEYWORDS:

5′ UTR regulatory elements; IRES elements; SRM; gene regulation; internal ribosome entry site elements; ribosome heterogeneity; selected reaction monitoring; translational control

PMID:
28625553
PMCID:
PMC5548184
DOI:
10.1016/j.molcel.2017.05.021
[Indexed for MEDLINE]
Free PMC Article

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