Laboratory of Neuroembryology at CERC

Santa Lucia di Serino, Italy

Laboratory of Neuroembryology at CERC

Santa Lucia di Serino, Italy

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Paronetto M.P.,Laboratory of Neuroembryology at CERC | Sette C.,University of Rome Tor Vergata
International Journal of Andrology | Year: 2010

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 differentiation 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 inactive stages of spermatogenesis. Germ cells express high levels of RNA-binding proteins that assist these post-transcriptional events. The generation of mouse knockout models has highlighted the essential role played by many of these RNA-binding proteins for the correct progress of spermatogenesis and for the formation of a fertile male gamete. Herein, we review the major findings on the role of RNA-binding proteins in mammalian spermatogenesis. © 2010 European Academy of Andrology.


Pedrotti S.,University of Rome Tor Vergata | Pedrotti S.,Laboratory of Neuroembryology at CERC | Bielli P.,University of Rome Tor Vergata | Bielli P.,Laboratory of Neuroembryology at CERC | And 7 more authors.
EMBO Journal | Year: 2010

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of motor neurons in patients with null mutations in the SMN1 gene. An almost identical SMN2 gene is unable to compensate for this deficiency because a single C-to-T transition at position 6 in exon-7 causes skipping of the exon by a mechanism not yet fully elucidated. We observed that the C-to-T transition in SMN2 creates a putative binding site for the RNA-binding protein Sam68. RNA pull-down assays and UV-crosslink experiments showed that Sam68 binds to this sequence. In vivo splicing assays showed that Sam68 triggers SMN2 exon-7 skipping. Moreover, mutations in the Sam68-binding site of SMN2 or in the RNA-binding domain of Sam68 completely abrogated its effect on exon-7 skipping. Retroviral infection of dominant-negative mutants of Sam68 that interfere with its RNA-binding activity, or with its binding to the splicing repressor hnRNP A1, enhanced exon-7 inclusion in endogenous SMN2 and rescued SMN protein expression in fibroblasts of SMA patients. Our results thus indicate that Sam68 is a novel crucial regulator of SMN2 splicing. © 2010 European Molecular Biology Organization | All Rights Reserved.


PubMed | Laboratory of Neuroembryology at CERC
Type: Journal Article | Journal: International journal of andrology | Year: 2010

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 differentiation 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 inactive stages of spermatogenesis. Germ cells express high levels of RNA-binding proteins that assist these post-transcriptional events. The generation of mouse knockout models has highlighted the essential role played by many of these RNA-binding proteins for the correct progress of spermatogenesis and for the formation of a fertile male gamete. Herein, we review the major findings on the role of RNA-binding proteins in mammalian spermatogenesis.

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