Sette, Claudio

Firenze University Press: E-Journals

IJAE Vol. 115, n. 1/2 (Supplement), 2010
4
Control of spermatogenesis by transcriptional and 
post-transcriptional regulation of gene expression
Claudio Sette
 Department of Public Health and Cell Biology, University of Rome Tor Vergata, Italy
Spermatogenesis is a cell differentiation programme that allows a normally dividing 
diploid cell to become haploid and to acquire the morphological characteristics required 
to reach and to fertilize the female gamete. Many of the steps involved in this differentia-
tion programme necessitate profound modifications of the genome, rendering it unable 
to play its template role for the synthesis of mRNAs. Therefore, de novo transcription is 
not a continuous process during germ cell differentiation and many mRNAs need to be 
synthesized and stored at specific times to be available during the transcriptionally inac-
tive stages of spermatogenesis. Activation of signal transduction pathways orchestrate 
RNA metabolism at specific steps of spermatogenesis. In particular, translation of stored 
mRNAs accounts for protein synthesis during the transcriptionally inactive stages of 
spermatogenesis. A key step in mRNA translation is the assembly of the initiation com-
plex EIF4F, which is regulated by the mTOR and MNK pathways. By performing in vivo 
labeling studies we have shown that pachytene spermatocytes display higher rates of 
protein synthesis, which are partially dependent on mTOR and MNK activity. By con-
trast, haploid spermatids are characterized by lower levels of protein synthesis, which 
are independent of the activity of these pathways. Notably, external cues differentially 
modulated the activity of these pathways in meiotic and haploid cells. Thus, our results 
have demonstrated that translational regulation is differentially dependent on signal-
ling pathways during germ cell differentiation. 
An additional layer of regulation is provided by the high levels of expression of RNA-
binding proteins in germ cells. These proteins assist many post-transcriptional events 
in gene expression and the generation of mouse knockout models has highlighted the 
essential role played by these proteins for the correct progress of spermatogenesis and 
for the formation of a fertile male gamete. Our laboratory has contributed to the field by 
elucidating the role of Sam68 in the regulation of spermatogenesis. Sam68 is a KH-type 
RNA-binding protein involved in several steps of RNA metabolism with potential im-
plications in cell differentiation and cancer. We have shown that Sam68 knockout male 
mice are infertile and display several defects in spermatogenesis, demonstrating an es-
sential role for Sam68 in male fertility. Sam68 knockout mice produce few spermatozoa, 
which display dramatic motility defects and are unable to fertilize eggs. Expression of 
a subset of messenger mRNAs and of microRNAs is affected in the testis of knockout 
mice. Interestingly, Sam68 is associated with polyadenylated mRNAs in the cytoplasm 
during the meiotic divisions and in round spermatids, when it interacts with the trans-
lational machinery. We have described that Sam68 is required for polysomal recruitment 
of specific mRNAs and for accumulation of the corresponding proteins in germ cells 
and in a heterologous system. Thus, our observations have demonstrated a novel role 
for Sam68 in mRNA translation and have highlighted its essential requirement for the 
development of a functional male gamete.
5In conclusion, these studies illustrate how a tight control of RNA metabolism in-
sures the correct flow of gene expression in differentiating male germ cells, in spite of 
discontinuous rates of mRNA transcription due to the profound genomic modifications 
required for the production of a functional male gamete.


Control of spermatogenesis by transcriptional and post-transcriptional regulation of gene expression

http://www.fupress.net/index.php/ijae/article/download/8760/8153

Control of spermatogenesis by transcriptional and post-transcriptional regulation of gene expression

Abstract

Similar works

Full text

Available Versions

Firenze University Press: E-Journals