A role for the eukaryotic translation initiation factor eIF4E in maintaining the homeostasis of RNA polymerase II

Published: 23 July 2026| Version 1 | DOI: 10.17632/v5m8hjkc7m.1
Contributors:
Nanjaraj Urs Ankanahalli Nanjaraje Urs, Animesh Dali, Emily Wilkerson, Alana Plastrik, Kyusik Kim, Victor Lasehinde, Nima Mosammaparast, Dennis Goldfarb, Hani Zaher

Description

Unlike in prokaryotes, transcription and translation are physically separated in eukaryotes by the nuclear envelope. The translation initiation factor eIF4E, has additional nuclear functions during pre-mRNA processing and export. Here, we identify a previously unrecognized function of eIF4E in remodeling RNA polymerase II. Acute depletion of eIF4E triggers rapid degradation of the largest and second-largest RNAP II subunits, Rpb1 and Rpb2, while other subunits are left unchanged. This effect appears to depend on eIF4E cap-binding activity as it is phenocopied by inhibition of mRNA capping. Mechanistically, this pathway is distinct from canonical RNAP II degradation routes, as it depends neither on ubiquitination by the Elongin-Cullin system nor extraction by Cdc48/VCP. Instead, our data implicates the E3 ligase Asr1, which recognizes Ser5/Ser7-hyperphosphorylated CTD of RNAP II. We propose that this mechanism evolved in eukaryotes as a safeguard to ensure that the flux of transcription is fine-tuned to that of translation.

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Biochemistry, Molecular Biology, Gene Expression Control, Transcription, Protein Synthesis, RNA Polymerase, Initiation Complex, Ubiquitin Ligase

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