Understanding the Role of Minor Intron Splicing in Spermatogenesis

The minor spliceosome is composed of the unique small nuclear RNAs (snRNA), U11, U12, U4atac, and U6atac, and is necessary for the splicing of less than 0.5% of introns, termed minor introns. Minor intron containing genes (MIGs) regulate diverse processes, one of which is spermatogenesis. Specifically, 111 testis-specific MIGs have been identified, suggesting that minor splicing is necessary for spermatogenesis. To interrogate the role of minor splicing in spermatogenesis, we conditionally ablated the Rnu11 gene, which encodes for the U11 snRNA, in the developing testes via Stra8-iCre, creating a Rnu11Flx/Flx::Stra8-Cre+ mutant. We found, at postnatal day (p) 42, the mutant testes are smaller than the wildtype (WT). Assay for cell death confirmed that U11 ablation results in cell death in the mutant at 6 weeks of age. Lastly, we found that our mutant resulted in varying spermatogenesis defects, such as an increase of asynchronous meiosis and a decrease in differentiating cells. Despite this, meiotic recombination can still occur in these mutants, concluding that U11 is important but not essential for meiotic recombination. This work is the first study to assess the importance of minor splicing in spermatogenesis which is underscored by the phenotype observed when the minor spliceosome is inhibited. Furthermore, the importance of studying spermatogenesis is highlighted by a decrease in sperm count over the last decades, which contributes to rising rates of male infertility

Understanding the Role of Minor Intron Splicing in Spermatogenesis

The minor spliceosome is composed of the unique small nuclear RNAs (snRNA), U11, U12, U4atac, and U6atac, and is necessary for the splicing of less than 0.5% of introns, termed minor introns. Minor intron containing genes (MIGs) regulate diverse processes, one of which is spermatogenesis. Specifically, 111 testis-specific MIGs have been identified, suggesting that minor splicing is necessary for spermatogenesis. To interrogate the role of minor splicing in spermatogenesis, we conditionally ablated the Rnu11 gene, which encodes for the U11 snRNA, in the developing testes via Stra8-iCre, creating a Rnu11Flx/Flx::Stra8-Cre+ mutant. We found, at postnatal day (p) 42, the mutant testes are smaller than the wildtype (WT). Assay for cell death confirmed that U11 ablation results in cell death in the mutant at 6 weeks of age. Lastly, we found that our mutant resulted in varying spermatogenesis defects, such as an increase of asynchronous meiosis and a decrease in differentiating cells. Despite this, meiotic recombination can still occur in these mutants, concluding that U11 is important but not essential for meiotic recombination. This work is the first study to assess the importance of minor splicing in spermatogenesis which is underscored by the phenotype observed when the minor spliceosome is inhibited. Furthermore, the importance of studying spermatogenesis is highlighted by a decrease in sperm count over the last decades, which contributes to rising rates of male infertility

Resumos concluídos - Bioquímica

Resumos concluídos - Bioquímic

Resumos concluídos - Bioquímica

Resumos concluídos - Bioquímic

Charged-particle multiplicity distributions over a wide pseudorapidity range in proton-proton collisions at √s = 0.9, 7 and 8 TeV

We present the charged-particle multiplicity distributions over a wide pseudorapidity range (−3.4<η<5.0) for pp collisions at s√= 0.9, 7, and 8 TeV at the LHC. Results are based on information from the Silicon Pixel Detector and the Forward Multiplicity Detector of ALICE, extending the pseudorapidity coverage of the earlier publications and the high-multiplicity reach. The measurements are compared to results from the CMS experiment and to PYTHIA, PHOJET and EPOS LHC event generators, as well as IP-Glasma calculations

Charged-particle multiplicity distributions over a wide pseudorapidity range in proton-proton collisions at √s = 0.9, 7, and 8 TeV

We present the charged-particle multiplicity distributions over a wide pseudorapidity range (−3.4<η<5.0) for pp collisions at s√=0.9,7, and 8 TeV at the LHC. Results are based on information from the Silicon Pixel Detector and the Forward Multiplicity Detector of ALICE, extending the pseudorapidity coverage of the earlier publications and the high-multiplicity reach. The measurements are compared to results from the CMS experiment and to PYTHIA, PHOJET and EPOS LHC event generators, as well as IP-Glasma calculations