A possible meiotic function of the peculiar patterns of gene expression in mammalian spermatogenic cells

Abstract

This review focuses on the striking differences in the patterns of transcription and translation in somatic and spermatogenic cells in mammals. In early haploid cells, mRNA translation evidently functions to restrict the synthesis of certain proteins, notably protamines, to transcriptionally inert late haploid cells. However, this does not explain why a substantial proportion of virtually all mRNA species are sequestered in translationally inactive free-messenger ribonucleoprotein particles (free-mRNPs) in meiotic cells, since most mRNAs undergo little or no increase in translational activity in transcriptionally active early haploid cells. In addition, most mRNAs in meiotic cells appear to be overexpressed because they are never fully loaded on polysomes and the levels of the corresponding protein are often much lower than the mRNA and are sometimes undetectable. A large number of genes are expressed at grossly higher levels in meiotic and/or early haploid spermatogenic cells than in somatic cells, yet they too are translated inefficiently. Many genes utilize alternative promoters in somatic and spermatogenic cells. Some of the resulting spermatogenic cell-altered transcripts (SCATs) encode proteins with novel functions, while others contain features in their 5'-UTRs, secondary structure or upstream reading frames, that are predicted to inhibit translation. This review proposes that the transcriptional machinery is modified to provide access to specific DNA sequences during meiosis, which leads to mRNA overexpression and creates a need for translational fine-tuning to prevent deleterious consequences of overproducing proteins.

Sex-specific promoters regulate Dnmt3L expression in mouse germ cells

“…For many of these genes, such as SOD-1 (Gu and Hecht, 1996), Cytochrome C (Hake and Hecht, 1993), Proenkephalin (Rao and Howells, 1993) and Dnmt1 (Trasler et al, 1992;Mertineit et al, 1998), the presence of additional sequences in the 5′ untranslated region has been shown to correlate with low or undetectable protein. As in the case of Dnmt3L, production of a pachytene-specific transcript for α-tubulin lacking any ORF is conserved across species, suggesting that these non-coding transcripts have important functions (Kleene, 2001). Conservation of adult testis transcript production for Dnmt3L between humans and mice strongly suggest that these may play an important role in regulating production of the full-length protein in round spermatids.…”

“…These transcripts are unlikely to produce a functional protein, because the only ORF in-frame with the Dnmt3L protein has an ATG which does not match the Kozak consensus sequence, is preceded by multiple upstream ORFs and is not conserved between mice and humans. There are a number of other genes that utilize an alternative promoter to produce a different transcript during late meiosis or round spermatid stages in male germ cells (see Kleene, 2001 for a recent review). For many of these genes, such as SOD-1 (Gu and Hecht, 1996), Cytochrome C (Hake and Hecht, 1993), Proenkephalin (Rao and Howells, 1993) and Dnmt1 (Trasler et al, 1992;Mertineit et al, 1998), the presence of additional sequences in the 5′ untranslated region has been shown to correlate with low or undetectable protein.…”

Aquaporins in spermatozoa and testicular germ cells: identification and potential role

“…Because of chromatin packaging during spermiogenesis, proteins used for the formation of spermatozoa in the testis have to be synthesized by the latest in elongating spermatids [48], by delayed translation (uncoupled from transcription), before the mRNA is degraded as spermiogenesis progresses [49]. As mature spermatozoa do not undergo conventional gene transcription and translation, possess a condensed nucleus and sparse cytoplasm, any presence of mRNA of existing proteins only represents remnants from the spermatid [50].…”

Expression profiling reveals meiotic male germ cell mRNAs that are translationally up- and down-regulated

“…Pgk2 mRNAs are sequestered as RNPs in pachytene spermatocytes and, with continued transcription, move onto polysomes in later stage spermatids (11,(23)(24)(25). By using Pgk2 as a marker mRNA to detect populations of mRNAs showing similar meiotic expression and translational delays, Ͼ70% of Pgk2 mRNA fractionates as RNPs in the testes of 17-day-old and 22-day-old mice and redistributes onto polysomes in adult mice (Table 10).…”