Project description:A bifunctional snoRNA with separable activities in guiding rRNA 2'-O-methylation and scaffolding gametogenic effectors (total and polyA RNA-Seq)
Project description:Small nucleolar RNAs (snoRNAs) are non-coding transcripts that guide chemical modifications of RNA substrates and contribute to gene expression at the epigenetic and post-transcriptional levels. However, the extent of their regulatory potential and the underlying molecular mechanisms remain poorly understood. Here, we identify a previously unannotated intronic C/D-box snoRNA, termed snR107, hosted in the fission yeast long non-coding RNA (lncRNA) mamRNA and carrying two independent cellular functions. On one hand, snR107 guides site-specific 25S rRNA 2’-O-methylation and promotes pre-rRNA processing/60S subunit biogenesis. On the other hand, snR107 associates with the gametogenic RNA-binding proteins Mmi1 and Mei2, mediating their reciprocal inhibition and restricting meiotic gene expression during sexual differentiation. Both functions require distinct cis-motifs within snR107, including a conserved 2’-O-methylation guiding sequence. Together, our results position snR107 as a dual regulator of rRNA modification and gametogenesis effectors, expanding our vision on the non-canonical functions exerted by snoRNAs in cell fate decisions.
Project description:Small nucleolar RNAs (snoRNAs) are non-coding transcripts that guide chemical modifications of RNA substrates and contribute to gene expression at the epigenetic and post-transcriptional levels. However, the extent of their regulatory potential and the underlying molecular mechanisms remain poorly understood. Here, we identify a previously unannotated intronic C/D-box snoRNA, termed snR107, hosted in the fission yeast long non-coding RNA (lncRNA) mamRNA and carrying two independent cellular functions. On one hand, snR107 guides site-specific 25S rRNA 2’-O-methylation and promotes pre-rRNA processing/60S subunit biogenesis. On the other hand, snR107 associates with the gametogenic RNA-binding proteins Mmi1 and Mei2, mediating their reciprocal inhibition and restricting meiotic gene expression during sexual differentiation. Both functions require distinct cis-motifs within snR107, including a conserved 2’-O-methylation guiding sequence. Together, our results position snR107 as a dual regulator of rRNA modification and gametogenesis effectors, expanding our vision on the non-canonical functions exerted by snoRNAs in cell fate decisions.
Project description:Small nucleolar RNAs (snoRNAs) are non-coding transcripts that guide chemical modifications of RNA substrates and contribute to gene expression at the epigenetic and post-transcriptional levels. However, the extent of their regulatory potential and the underlying molecular mechanisms remain poorly understood. Here, we identify a previously unannotated intronic C/D-box snoRNA, termed snR107, hosted in the fission yeast long non-coding RNA (lncRNA) mamRNA and carrying two independent cellular functions. On one hand, snR107 guides site-specific 25S rRNA 2’-O-methylation and promotes pre-rRNA processing/60S subunit biogenesis. On the other hand, snR107 associates with the gametogenic RNA-binding proteins Mmi1 and Mei2, mediating their reciprocal inhibition and restricting meiotic gene expression during sexual differentiation. Both functions require distinct cis-motifs within snR107, including a conserved 2’-O-methylation guiding sequence. Together, our results position snR107 as a dual regulator of rRNA modification and gametogenesis effectors, expanding our vision on the non-canonical functions exerted by snoRNAs in cell fate decisions.
Project description:Purpose: To find out the patients who are most sensitive and effective to the anti-PD-L1 and TGF-β bifunctional fusion protein in the treatment of recurrent cervical cancer. Patients and methods: We report two cases of recurrent cervical cancer treated with the anti-PD-L1 and TGF-β bifunctional fusion protein. We described the clinical course, clinical characteristics, and genetic characteristics of the two patients, and analyzed the changes of gene expression in the two patients after treatment. Results: Although PD-L1 expression and HPV status were same in the two patients, the treatment effect of two patients with recurrent cervical cancer was different, according to the evaluation of enhanced computed tomography (CT), one was partial response (PR) and the other was progressive disease (PD), which may indicate that PD-L1 expression and HPV status of patients is not enough to predict the effectiveness of the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Then, we demonstrated that the changes of peripheral blood lymphocytes of two patients during the treatment had different trends. Moreover, number of alterable genes in PR patient is much greater than that in PD patient, indicating PR patient may be more sensible to the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Total 4844 genes changing-fate gene set selected which is believed conducting anti-cancer function during the anti-PD-L1 and TGF-β bifunctional fusion protein treatments. Furthermore, we identified that changing-fate genes were correlated with female reproductive organ cancer, infectious disease, inflammatory disease, immune system, indicating these genes may conducting anti-cancer, anti-inflammation and immune function. Conclusion: Anti-PD-L1 and TGF-β bifunctional fusion protein is feasible for the treatment of recurrent cervical cancer. Multi-center, large-sample prospective clinical studies are still needed to further explore the efficacy of anti-PD-L1 and TGF-β bifunctional fusion protein in recurrent cervical cancer and screen appropriate patients, so as to achieve the maximum survival benefit of patients.
Project description:The epigenetic mechanisms that enable specialized astrocytes to retain neurogenic competence throughout adult life are still poorly understood. Here we show that astrocytes that serve as neural stem cells (NSCs) in the adult mouse subventricular zone (SVZ) express the histone methyltransferase EZH2. This Polycomb repressive factor is required for neurogenesis independent of its role in SVZ NSC proliferation, as Ink4a/Arf-deficiency in Ezh2-deleted SVZ NSCs rescues cell proliferation, but neurogenesis remains defective. Olig2 is a direct target of EZH2, and repression of this bHLH transcription factor is critical for neuronal differentiation. Furthermore, Ezh2 prevents the inappropriate activation of genes that specify non-SVZ neuronal subtypes. In the human brain, SVZ cells including local astroglia also express EZH2, correlating with postnatal neurogenesis. Thus, EZH2 is an epigenetic regulator that distinguishes neurogenic SVZ astrocytes, orchestrating distinct and separable aspects of adult stem cell biology, which has important implications for regenerative medicine and oncogenesis. Examination of histone modifications (H3K27me3 and H3K4me3) in subventricular zone neural stem cells