Open AccessTDRD6 mediates early steps of spliceosome maturation in primary spermatocytes
Author(s) -
Müge Akpınar,
Mathias Lesche,
Grigorios Fanourgakis,
Jun Fu,
Konstantinos Anastassiadis,
Andreas Dahl,
Rolf Jessberger
Publication year - 2017
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1006660
Subject(s) - spliceosome , biology , cajal body , snrnp , rna splicing , spermatid , microbiology and biotechnology , intron , meiocyte , genetics , protein arginine methyltransferase 5 , prophase , rna binding protein , meiosis , rna , methylation , sperm , gene , methyltransferase
Tudor containing protein 6 (TDRD6) is a male germ line-specific protein essential for chromatoid body (ChB) structure, elongated spermatid development and male fertility. Here we show that in meiotic prophase I spermatocytes TDRD6 interacts with the key protein arginine methyl transferase PRMT5, which supports splicing. TDRD6 also associates with spliceosomal core protein SmB in the absence of RNA and in an arginine methylation dependent manner. In Tdrd6 -/- diplotene spermatocytes PRMT5 association with SmB and arginine dimethylation of SmB are much reduced. TDRD6 deficiency impairs the assembly of spliceosomes, which feature 3.5-fold increased levels of U5 snRNPs. In the nucleus, these deficiencies in spliceosome maturation correlate with decreased numbers of SMN-positive bodies and Cajal bodies involved in nuclear snRNP maturation. Transcriptome analysis of TDRD6-deficient diplotene spermatocytes revealed high numbers of splicing defects such as aberrant usage of intron and exons as well as aberrant representation of splice junctions. Together, this study demonstrates a novel function of TDRD6 in spliceosome maturation and mRNA splicing in prophase I spermatocytes.