Abstract

Rtr1 is an RNA polymerase II (RNA pol II) CTD-phosphatase that influences gene expression during the transition from transcription initiation to elongation and during transcription termination. Rtr1 interacts with the RNA pol II and this interaction depends on the phosphorylation state of the CTD of Rpb1, which may influence dissociation of the heterodimer Rpb4/7 during transcription. In addition, Rtr1 was proposed as an RNA pol II import factor in RNA pol II biogenesis and participates in mRNA decay by autoregulating the turnover of its own mRNA. Our work shows that Rtr1 acts in RNA pol II assembly by mediating the Rpb4/7 association with the rest of the enzyme. RTR1 deletion alters RNA pol II assembly and increases the amount of RNA pol II associated with the chromatin that lacks Rpb4, decreasing Rpb4-mRNA imprinting and, consequently, increasing mRNA stability. Thus, Rtr1 interplays RNA pol II biogenesis and mRNA decay regulation. Our data also indicate that Rtr1 mediates mRNA decay regulation more broadly than previously proposed by cooperating with Rpb4. Interestingly, our data include new layers in the mechanisms of gene regulation and in the crosstalk between mRNA synthesis and decay by demonstrating how the association of Rpb4/7 to the RNA pol II influences mRNA decay.

Highlights

  • Published: 11 February 2022RNA polymerase II (RNA pol II) is composed of a 10-subunit core polymerase and the dissociable heterodimer Rpb4 and Rpb7 in Saccharomyces cerevisiae [1,2,3]

  • The Presence of Rpb4 in the Chromatin-Associated RNA Polymerase II Depends on Rtr1

  • Rtr1 and its human counterpart RPAP2 participate in the biogenesis of RNA pol II by facilitating its transport from the cytoplasm to the nucleus [45,51]

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Summary

Introduction

Published: 11 February 2022RNA polymerase II (RNA pol II) is composed of a 10-subunit core polymerase and the dissociable heterodimer Rpb and Rpb in Saccharomyces cerevisiae [1,2,3]. Rpb4/7 binds mRNA cotranscriptionally, influencing mRNA export, translation, and decay [11,12,13,14,15,16,17,18]. It is assumed that gene expression ensures appropriate mRNA levels, which maintains mRNA homeostasis by coordinating transcription in the nucleus, and mRNA decay, which occurs mainly in the cytoplasm [23,24,25,26]. Some authors define gene expression as a circular process during which the synthesis and degradation of mRNAs are coordinated in a process called the crosstalk of mRNA, which extends the classic view of the Central

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