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Cstf2t Regulates expression of histones and histone‐like proteins in male germ cells
Author(s) -
Grozdanov P. N.,
Li J.,
Yu P.,
Yan W.,
MacDonald C. C.
Publication year - 2018
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12488
Subject(s) - polyadenylation , biology , cleavage stimulation factor , cleavage and polyadenylation specificity factor , rna binding protein , messenger rna , histone , microbiology and biotechnology , immunoprecipitation , gene , genetics
Summary Formation of the 3′ ends of mature mRNA s requires recognition of the correct site within the last exon, cleavage of the nascent pre‐ mRNA , and, for most mRNA s, 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 mRNA s 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 mRNA s during male germ cell formation.