title: TDRD6 mediates early steps of spliceosome maturation in primary spermatocytes.
abstract: 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.
authors.affiliation: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Müge
authors.initials: M
authors.lastname: Akpınar
authors.affiliation: Deep Sequencing Group SFB 655, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Mathias
authors.identifier: 0000-0002-3274-7163
authors.initials: M
authors.lastname: Lesche
authors.affiliation: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Grigorios
authors.initials: G
authors.lastname: Fanourgakis
authors.affiliation: Stem Cell Engineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.affiliation: Stem Cell Engineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Anastassiadis
authors.affiliation: Deep Sequencing Group SFB 655, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dahl
authors.affiliation: Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Rolf
authors.identifier: 0000-0002-2972-2192
authors.initials: R
authors.lastname: Jessberger
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D002842:Chromatids / Q000737:chemistry; D020541:Coiled Bodies / Q000378:metabolism; D019175:DNA Methylation; D003839:Deoxyadenosines / Q000737:chemistry; D005091:Exons; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D007438:Introns; D008297:Male; D008745:Methylation; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D000072417:Protein Domains; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D017415:Ribonucleoprotein, U5 Small Nuclear / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics* / Q000502:physiology*; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism*; D017381:Spliceosomes / Q000378:metabolism*; D013872:Thionucleosides / Q000737:chemistry; D059467:Transcriptome
chemical_list: D003839:Deoxyadenosines; D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; D017415:Ribonucleoprotein, U5 Small Nuclear; D012261:Ribonucleoproteins; C517521:TDRD6 protein, mouse; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D001120:Arginine; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases; C038753:leptomycin B