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UBAP2/UBAP2L regulate UV-induced ubiquitylation of RNA polymerase II and are the human orthologues of yeast Def1

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posted on 27.05.2022, 10:20 authored by Anna E Herlihy, Stefan Boeing, Juston C Weems, Jane Walker, A Barbara Dirac-Svejstrup, Michelle Harreman Lehner, Ronald C Conaway, Joan W Conaway, Jesper Q Svejstrup
During transcription, RNA polymerase II (RNAPII) faces numerous obstacles, including DNA damage, which can lead to stalling or arrest. One mechanism to contend with this situation is ubiquitylation and degradation of the largest RNAPII subunit, RPB1 - the ‘last resort’ pathway. This conserved, multi-step pathway was first identified in yeast, and the functional human orthologues of all but one protein, RNAPII Degradation Factor 1 (Def1), have been discovered. Here we show that following UV-irradiation, human Ubiquitin-associated protein 2 (UBAP2) or its paralogue UBAP2-like (UBAP2L) are involved in the ubiquitylation and degradation of RNAPII through the recruitment of Elongin-Cul5 ubiquitin ligase. Together, our data indicate that UBAP2 and UBAP2L are the human orthologues of yeast Def1, and so identify the key missing proteins in the human last resort pathway.

Funding

Crick (Grant ID: 10002, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: 10166, Grant title: Svejstrup FC001166) European Research Council (Grant ID: 693327 - TRANSDAM, Grant title: ERC 693327 - TRANSDAM)

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