RNA polymerase II CTD S2P is dispensable for embryogenesis but mediates exit from developmental diapause in C. elegans

C. Cassart, C. Yague-Sanz, F. Bauer, P. Ponsard, F. X. Stubbe, V. Migeot, M. Wery, A. Morillon, F. Palladino, V. Robert, D. Hermand

Research output: Contribution to journalArticlepeer-review

Abstract

Serine 2 phosphorylation (S2P) within the CTD of RNA polymerase II is considered a Cdk9/Cdk12-dependent mark required for 3′-end processing. However, the relevance of CTD S2P in metazoan development is unknown. We show that cdk-12 lesions or a full-length CTD S2A substitution results in an identical phenotype in Caenorhabditis elegans. Embryogenesis occurs in the complete absence of S2P, but the hatched larvae arrest development, mimicking the diapause induced when hatching occurs in the absence of food. Genome-wide analyses indicate that when CTD S2P is inhibited, only a subset of growth-related genes is not properly expressed. These genes correspond to SL2 trans-spliced mRNAs located in position 2 and over within operons. We show that CDK-12 is required for maximal occupancy of cleavage stimulatory factor necessary for SL2 trans-splicing. We propose that CTD S2P functions as a gene-specific signaling mark ensuring the nutritional control of the C. elegans developmental program.

Original languageEnglish
Article numbereabc1450
JournalScience Advances
Volume6
Issue number50
DOIs
Publication statusPublished - 1 Dec 2020

Funding

ts: We thank F. Steiner for many insightful discussions and O. Finet for critical reading of the manuscript. We thank T. Blumenthal for the anti\u2013CPF-1 and anti\u2013CPF-2 antibodies. C.C., C.Y.-S., and F.X.S. were supported by a FRIA fellowship. This work has benefited from the facilities and expertise of the NGS platform of Institut Curie, supported by the grants ANR-10-EQPX-03 and ANR10-INBS-09-08 and by the Cancerop\u00F4le Ile-de-France. This work was supported by grants ANR-15-CE12-0007 and ERC consolidator \u201CDARK\u201D to A.M. and by grants MIS F.4523.11, PDR T.0012.14, and CDR J.0066.16 to D.H. D.H. is an FNRS Research Director.

FundersFunder number
ANR-15-CE12-0007
Cancéropôle Ile de France
Fonds De La Recherche Scientifique - FNRS
Agence Nationale de la RechercheANR-15-CE12-0007
European Resuscitation CouncilMIS F.4523.11, PDR T.0012.14, CDR J.0066.16
Fonds pour la Formation à la Recherche dans l’Industrie et dans l’AgricultureANR-10-EQPX-03, ANR10-INBS-09-08

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