Faculty Collaboration Database

Noncanonical translation via deadenylated 3' UTRs maintains primordial germ cells. Nat Chem Biol 2018 Sep;14(9):844-852

Date

07/11/2018

Pubmed ID

29988067

Pubmed Central ID

PMC6800240

DOI

10.1038/s41589-018-0098-0

Scopus ID

2-s2.0-85049618175 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Primordial germ cells (PGCs) form during early embryogenesis with a supply of maternal mRNAs that contain shorter poly(A) tails. How translation of maternal mRNAs is regulated during PGC development remains elusive. Here we describe a small-molecule screen with zebrafish embryos that identified primordazine, a compound that selectively ablates PGCs. Primordazine's effect on PGCs arises from translation repression through primordazine-response elements in the 3' UTRs. Systematic dissection of primordazine's mechanism of action revealed that translation of mRNAs during early embryogenesis occurs by two distinct pathways, depending on the length of their poly(A) tails. In addition to poly(A)-tail-dependent translation (PAT), early embryos perform poly(A)-tail-independent noncanonical translation (PAINT) via deadenylated 3' UTRs. Primordazine inhibits PAINT without inhibiting PAT, an effect that was also observed in quiescent, but not proliferating, mammalian cells. These studies reveal that PAINT is an alternative form of translation in the early embryo and is indispensable for PGC maintenance.

Author List

Jin YN, Schlueter PJ, Jurisch-Yaksi N, Lam PY, Jin S, Hwang WY, Yeh JJ, Yoshigi M, Ong SE, Schenone M, Hartigan CR, Carr SA, Peterson RT

Author

Pui Ying Lam PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3' Untranslated Regions
Animals
Cell Line, Tumor
Germ Cells
Hydrazines
Mice
Peptide Chain Initiation, Translational
Zebrafish