Transcriptional and translational regulation of gene expression in haploid spermatids

Abstract

During spermiogenesis, round spermatids undergo complex morphological, biochemical, and physiological modifications resulting in the formation of mature spermatozoa. While in round spermatids histones and non-histone proteins are replaced by transition proteins, in elongating spermatids, transition proteins are removed from the condensing chromatin and are replaced by protamines, which are the principal basic nuclear proteins of mature spermatozoa. The tightly packed DNA-protamine complexes cease transcription several days before the completion of spermiogenesis. Thus, major modifications in both nuclear and cytoplasmic structures continue throughout spermiogenesis, stringent temporal and stage-specific gene expression is a prerequisite for the correct differentiation of round spermatids into mature spermatozoa. The genes for transition proteins and protamines are transcribed in round and elongating spermatids. Transcription is regulated via methylation and trans-acting factors that bind to the TATA-box, the CRE-box, or other specific DNA sequences in the promoter region. The transcripts are stored as ribonucleoprotein particles in a translationally repressed state for several days and are translated in elongating and elongated spermatids. It has been demonstrated that, in haploid spermatids, essentially every mRNA exhibits evidence of translational repression. Translational regulation involves protein repressors that bind to the poly-A tail or specific RNA sequences located in the 3'-UTR.

The E2 Ubiquitin-conjugating Enzyme UBE2J1 Is Required for Spermiogenesis in Mice

“…UBE2J1 protein was abundantly present in elongating spermatids, specifically from step 12 to 15 of sperm differentiation (31), peaking at step 14. Spermatids at these differentiation steps are largely transcriptionally inactive (32,33), implying that the transcripts are transcribed earlier, and that translation of the Ube2j1 (and presumably other) transcripts is de-repressed in elongate spermatids (34). Thus, UBE2J1 is likely required at a critical time within the elongating spermatid itself for successful completion of the final steps of differentiation and spermiation.…”

Identification of Genetic Variation in the 5′ and 3′ Non-coding Regions of the Protamine Genes in Patients with Protamine Deregulation

“…Humans express two types of protamines, protamine 1 (P1) and protamine 2 (P2), expressed in the post-meiotic haploid spermatid and stored in messenger ribonuclear protein (mRNP) particles [Steger et al 1998;Steger 1999], and translated in the elongating spermatid [Steger 2001;Steger et al 2002]. The temporal uncoupling of transcription and translation prevents precocious chromatin condensation and spermatogenic arrest [Lee et al 1995].…”

GDNF Signaling Regulates YBX1/mRNA Interactions in Mouse Spermatogonia.

“…One unique occurrence in spermatogenic cells that necessitates mRNA storage is the condensation of the chromatin in late spermatogenesis. In spermatids, transcription ceases, as does RNA processing, because histones are replaced by transition proteins and then protamines which tightly condense the DNA to fit in the sperm head [150][151][152][153].…”

“…Conserved small RNAs, families of proteins, and subcellular structures are involved in controlling the timing and efficiency of translation. Whether mechanisms other than mRNA storage through germline development necessitating translational regulation exist is not known, but whatever the cause, the extent of post-transcriptional regulation is high in male germ cells; nearly 70% of testis mRNAs are found in non-translated ribonucleoprotein particles (RNPs) [150].…”