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.
Highlights
Spermatogenesis is essential for the generation of haploid male gametes required for sexual reproduction in higher eukaryotes
The data reported here suggest a novel function for TDRD6 in the maturation of spliceosomal Small nuclear ribonucleoproteins (snRNPs) during the transcriptionally highly active prophase I of spermatogenesis
This function adds to the roles of TDRD6 at later stages of spermatogenesis/spermiogenesis in formation of the chromatoid body (ChB) type 2 and in nonsense-mediated decay
Summary
Spermatogenesis is essential for the generation of haploid male gametes required for sexual reproduction in higher eukaryotes. In the first meiotic division (meiosis I), pairs of homologous chromosomes are segregated and primary spermatocytes are reduced in chromosome content to diploid secondary spermatocytes (2N). These 2N cells undergo reduction to haploid spermatids (N) in the second meiotic division (meiosis II) through a mitosis-like division segregation of sister chromatids. Meiotic prophase I is by far the longest phase of meiosis, lasting approximately three weeks in most mammals. It is described by four sequential substages, i.e. leptotene, zygotene, pachytene and diplotene. Two successive meiotic divisions follow prophase I to produce haploid spermatids leading to the last stage of spermatogenesis called spermiogenesis; i.e. the process of morphological differentiation of haploid round spermatids to elongated spermatids to motile sperm
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