Paip2 cooperates with Cbp80 at an active promoter and participates in RNA Polymerase II phosphorylation in Drosophila

Abstract

The Paip2 protein is a factor regulating mRNA translation and stability in the cytoplasm. It has also been found in the nuclei of several cell types in Drosophila. Here, we aim to elucidate the functions of Paip2 in the cell nucleus. We find that nuclear Paip2 is a component of an ~300‐kDa protein complex. Paip2 interacts with mRNA capping factor and factors of RNA polymerase II (Pol II) transcription initiation and early elongation. Paip2 functionally cooperates with the Cbp80 subunit of the cap‐binding complex, with both proteins ensuring proper Pol II C‐terminal domain (CTD) Ser5 phosphorylation at the promoter. Thus, Paip2 is a novel player at the stage of mRNA capping and early Pol II elongation.

Transcriptional Coactivator PGC-1α Binding to Newly Synthesized RNA via CBP80: A Nexus for Co- and Posttranscriptional Gene Regulation

“…Of these functions, how the CBC promotes transcription is not well-characterized, especially in higher eukaryotes. To date, CBC-dependent transcription re-initiation has been established for Saccharomyces cerevisiae (Lahudkar et al 2011;Li et al 2016a) and Drosophila melanogaster (Kachaev et al 2019). Additionally, CBCdependent transcription elongation has been shown for S. cerevisiae (Hossain et al 2013;Lidschreiber et al 2013) and mammalian cells (Lenasi et al 2011).…”

“…Additionally, CBCdependent transcription elongation has been shown for S. cerevisiae (Hossain et al 2013;Lidschreiber et al 2013) and mammalian cells (Lenasi et al 2011). Notably, CBC-mediated control of transcription appears to be genespecific, and gene-specific molecular determinants of CBC-mediated re-initiation of transcription have been identified (Lahudkar et al 2011;Li et al 2016a;Kachaev et al 2019). However, how the CBC recruits elongation factors, such as the positive transcription elongation factor P-TEFb and the cyclin-dependent kinase CDK12, on specific genes is unknown (Lenasi et al 2011;Hossain et al 2013;Lidschreiber et al 2013).…”

The nuclear cap-binding complex as choreographer of gene transcription and pre-mRNA processing

“…In Drosophila melanogaster, knockdown (KD) of Cbp80 decreases total RNAPII occupancy at the promoter of inducible genes while increasing occupancy of initiating RNAPII(pS5) relative to elongating RNAPII(pS2) (Kachaev et al 2019). These results indicate that fruit fly Cbp80 not only promotes transcription (re)initiation but also facilitates release from promoter-proximal pausing.…”

“…These results indicate that fruit fly Cbp80 not only promotes transcription (re)initiation but also facilitates release from promoter-proximal pausing. Such coupling is proposed to be mediated by the interaction of Cbp80 with the poly(A)-binding protein-interacting protein 2 (Paip2) and the TBP-related factor Trf2 (Kachaev et al 2019). Interestingly, Cbp80-mediated expression of the fruit fly DHR3 gene following ecdysone treatment is associated with recruitment of Paip2 to only one of many alternative DHR3-gene promoters that is specifically induced by ecdysone (Kachaev et al 2019), raising the possibility that the CBC also participates in selecting alternative promoters through its interaction with Paip2.…”

Interplay of mRNA capping and transcription machineries

“…Recently, polyadenylate-binding protein-interacting protein 2 has been described as a novel partner of CBC. These proteins act jointly at the early elongation stage of transcription, and their depletion affects Ser 5 CTD Pol II phosphorylation in Drosophila [87,88].…”