Slowed decay of mRNAs enhances platelet specific translation

Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of messenger RNAs (mRNAs), ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the...

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Bibliographic Details
Published in:Blood 2017-04, Vol.129 (17), p.e38-e48
Main Authors: Mills, Eric W., Green, Rachel, Ingolia, Nicholas T.
Format: Article
Language:English
Subjects:
Blood Platelets - cytology
Blood Platelets - metabolism
Cell Differentiation
Endonucleases
Gene Expression Profiling
Gene Ontology
Humans
Megakaryocytes - cytology
Megakaryocytes - metabolism
Microfilament Proteins - genetics
Microfilament Proteins - metabolism
Molecular Sequence Annotation
Nuclear Proteins
Platelets and Thrombopoiesis
Primary Cell Culture
Protein Biosynthesis
Ribosomes - genetics
Ribosomes - metabolism
RNA Stability
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sequence Analysis, RNA
Transcriptome
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Summary:Platelets are anucleate cytoplasmic fragments that lack genomic DNA, but continue to synthesize protein using a pool of messenger RNAs (mRNAs), ribosomes, and regulatory small RNAs inherited from the precursor megakaryocyte (MK). The regulatory processes that shape the platelet transcriptome and the full scope of platelet translation have remained elusive. Using RNA sequencing (RNA-Seq) and ribosome profiling of primary human platelets, we show the platelet transcriptome encompasses a subset of transcripts detected by RNA-Seq analysis of in vitro–derived MK cells and that these platelet-enriched transcripts are broadly occupied by ribosomes. We use RNA-Seq of synchronized populations of in vitro–derived platelet-like particles to show that mRNA decay strongly shapes the nascent platelet transcriptome. Our data suggest that the decay of platelet mRNAs is slowed by the natural loss of the mRNA surveillance and ribosome rescue factor Pelota. •Ribosome profiling of primary human platelets defines the platelet translatome, derived from a biased subset of MK mRNAs.•Restoration of the ribosome rescue/mRNA surveillance factor Pelota, which is normally absent in wild-type platelets, promotes RNA decay.
ISSN:0006-4971
1528-0020
1528-0020
DOI:10.1182/blood-2016-08-736108