Requirement for cleavage factor IIm in the control of alternative polyadenylation in breast cancer cells.

Requirement for cleavage factor IIm in the control of alternative polyadenylation in breast cancer cells. RNA. 2020 Apr 15;: Authors: Turner RE, Henneken LM, Liem-Weits M, Harrison PF, Swaminathan A, Vary R, Nikolic I, Simpson KJ, Powell DR, Beilharz T, Dichtl B Abstract Alternative polyadenylation (APA) determines stability, localization and translation potential of the majority of mRNA in eukaryotic cells. The heterodimeric mammalian cleavage factor II (CF IIm) is required for pre-mRNA 3' end cleavage and is composed of the RNA kinase hClp1 and the termination factor hPcf11, the latter protein binds to RNA and the RNA polymerase II carboxy terminal domain. Here, we used siRNA mediated knock-down and poly(A) targeted RNA sequencing to analyze the role of CF IIm in gene expression and APA in estrogen receptor positive MCF7 breast cancer cells. Identified gene ontology terms link CF IIm function to regulation of growth factor activity, protein heterodimerization and the cell cycle. An overlapping requirement for hClp1 and hPcf11 suggested that CF IIm protein complex was involved in the selection of proximal poly(A) sites. In addition to APA shifts within 3' un-translated regions (3' UTRs) we observed shifts from promoter proximal regions to the 3' UTR facilitating synthesis of full-length mRNAs. Moreover, we show that several truncated mRNAs that resulted from APA within introns in MCF7 cells co-sedimented with ribosomal components in...
Source: RNA - Category: Genetics & Stem Cells Authors: Tags: RNA Source Type: research