Control of Messenger RNA Fate by RNA‐Binding Proteins: An Emphasis on Mammalian Spermatogenesis

Abstract

Posttranscriptional status of messenger RNAs (mRNA) can be affected by many factors, most of which are RNA-binding proteins (RBP) that either bind mRNA in a nonspecific manner or through specific motifs, usually located in the 39 untranslated regions. RBPs can also be recruited by small noncoding RNAs (sncRNA), which have been shown to be involved in posttranscriptional regulations and transposon repression (eg, microRNAs or P-element–induced wimpy testis–interacting RNA) as components of the sncRNA effector complex. Non–sncRNA-binding RBPs have much more diverse effects on their target mRNAs. Some can cause degradation of their target transcripts and/or repression of translation, whereas others can stabilize and/or activate translation. The splicing and exportation of transcripts from the nucleus to the cytoplasm are often mediated by sequence-specific RBPs. The mechanisms by which RBPs regulate mRNA transcripts involve manipulating the 39 poly(A) tail, targeting the transcript to polysomes or to other ribonuclear protein particles, recruiting regulatory proteins, or competing with other RBPs. Here, we briefly review the known mechanisms of posttranscriptional regulation mediated by RBPs, with an emphasis on how these mechanisms might control spermatogenesis in general.

Implication of transcriptome profiling of spermatozoa for stallion fertility

“…In post-meiotic spermatozoa, de novo transcription is silenced and the synthesis and storage of sufficient mRNA is very important to compensate for the lack of mRNAs during the subsequent transcriptionally inactive stage of spermatogenesis (Sassone-Corsi 2002). Germ cells have been shown to express high levels of RBPs throughout spermatogenesis, which are very essential to post-transcriptional events during all stages of spermatogenesis (Idler and Yan 2012). According to DAVID, in the present study three genes from the DE genes were involved in GO term 'RNA binding' (with P ¼ 0.05; Table 3).…”

“…They are involved in many cellular processes that occur during tissue development. Moreover, these proteins regulate immune response, the formation of dendrites and the differentiation of embryonic stem cells (Colegrove-Otero et al 2005;Idler and Yan 2012). RBPs are highly expressed during spermatogenesis and play an essential role during all stages of germ cell development.…”

“…Bettegowda and Wilkinson Miles (2010) reported the role of four RBPs, namely gonadotrophin-regulated testicular RNA helicase (GRTH), Src-associated in mitosis 68 kDa (SAM68), mouse Y-box protein 2 (MSY2) and deleted in azoospermiaassociated protein-1 (DAZAP1), that were shown to be critical for spermatogenesis by promoting the translation of a subset of germ cell mRNAs, indicating the importance of translation control for normal spermatogenesis. Furthermore, Idler and Yan (2012) reported that in mice, the inactivation of many of the RBPs studied caused infertility and spermatogenic arrest at various steps of germ cell differentiation.…”

Connecting cis-elements and trans-factors with mechanisms of developmental regulation of mRNA translation in meiotic and haploid mammalian spermatogenic cells

“…Translational regulation plays an important role in controlling the development of spermatocytes and spermatids (reviewed in Paronetto & Sette (2010), Nguyen-Chi & Morello (2011) and Idler & Yan (2012)). The most familiar example originates in chromatin remodeling in which histones are replaced by transition proteins and protamines during late spermiogenesis (reviewed in Meistrich et al (2003)).…”

“…Heterologous systems can produce interpretable results when the interaction between a factor and an element is sufficient to regulate translation, sometimes with the assistance of factors conveniently present in the heterologous cells (Ling et al 2002, Collier et al 2005. However, this approach is particularly risky with spermatogenic cells, which express many factors that differ qualitatively and quantitatively from those in somatic cells and oocytes (references in Kleene (2003), Nguyen-Chi & Morello (2011) and Idler & Yan (2012)). In some cases, the addition of a factor at a superphysiological level may alter translational activity only at excessive levels (see above) or the activity of the factor may depend on posttranslational modifications that are not fulfilled in the heterologous milieu.…”