Cstf2t Regulates expression of histones and histone‐like proteins in male germ cells. (19th April 2018)

• Record Type: Journal Article
• Authors: Grozdanov, P. N.; Li, J.; Yu, P.; Yan, W.; MacDonald, C. C.
• Is Part Of: Andrology. Volume 6:Number 4(2018)
• Page Start: 605
• Page End: 615
• Publication Date: 2018-04-19
• Subjects: H1fnt -- male germ cells -- polyadenylation -- protamine -- testis‐specific histone; Andrology -- Periodicals; 616.65
• DOI: 10.1111/andr.12488
• Languages: English
• ISSNs: 2047-2919

Abstract

Summary: Formation of the 3′ ends of mature mRNAs requires recognition of the correct site within the last exon, cleavage of the nascent pre‐mRNA, and, for most mRNAs, addition of a poly(A) tail. Several factors are involved in recognition of the correct 3′‐end site. The c leavage st imulation f actor (CstF) has three subunits, CstF‐50 (gene symbol Cstf1 ), CstF‐64 (Cstf2), and CstF‐77 (Cstf3) . Of these, CstF‐64 is the RNA‐binding subunit that interacts with the pre‐mRNA downstream of the cleavage site. In male germ cells where CstF‐64 is not expressed, a paralog, τCstF‐64 (gene symbol Cstf2t ) assumes its functions. Accordingly, Cstf2t knockout ( Cstf2t −/− ) mice exhibit male infertility due to defective development of spermatocytes and spermatids. To discover differentially expressed genes responsive to τCstF‐64, we performed RNA‐Seq in seminiferous tubules from wild‐type and Cstf2t −/− mice, and found that several histone and histone‐like mRNAs were reduced in Cstf2t −/− mice. We further observed delayed accumulation of the testis‐specific histone, H1fnt (formerly, H1t2 or Hanp1) in Cstf2t −/− mice. High‐throughput sequence analysis of polyadenylation sites (A‐seq) indicated reduced use of polyadenylation sites within a cluster downstream of H1fnt in knockout mice. However, high‐throughput sequencing of RNA isolated by cross‐linking immunoprecipitation (HITS‐CLIP) was not consistent with a direct role of τCstF‐64 in polyadenylation of H1fnt . These findings together suggest that the τCstF‐64 may control other reproductive functions that are not directly linked to the formation of 3′ ends of mature polyadenylated mRNAs during male germ cell formation.