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实验室

12:30-14:30, Friday, April 27, 2018


Speaker1: En-Zhi Shen, Ph.D.

Postdoctoral Research Associate,

RNA Therapeutics Institute,

University of Massachusetts Medical School

Topic:     Identification of piRNA Binding Sites Reveals the Argonaute Regulatory Landscape of the C. elegans Germline

Host:     Mengqiu Dong, Ph.D.

Abstract

piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting. In mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of piRNA associated secondary small RNAs. Our findings reveal physiologically important and nuanced regulation of individual piRNA targets and provide evidence for a comprehensive post-transcriptional regulatory step in germline gene expression.

Speaker2: Chun-Qing Song, Ph.D.

Postdoctoral Research Associate,

RNA Therapeutics Institute,

UMASS medical school

Topic:     In vivo Genome Editing with CRISPR/Cas9 in liver disease Host:     Mengqiu Dong, Ph.D.

Abstract

Using a CRISPR-based strategy, we identified Nf1, Plxnb1, Flrt2, and B9d1 as suppressors of liver tumor formation. We validated the observation that RAS signaling, via mitogen-activated protein kinase, contributes to formation of liver tumors in mice. We associated decreased levels of NF1 and increased levels of its downstream protein HMGA2 with survival times of patients with Hepatocellular Carcinoma. Strategies to inhibit or reduce HMGA2 might be developed to treat patients with liver cancer.

We used CRISPR-based strategy to correct genetic diseases including human hereditary tyrosinemia type I disease and human Alpha-1 Antitrypsin (AAT) deficiency in adult rodents. The results show that the treatment generated fumarylacetoacetate hydrolase (Fah)-positive hepatocytes by correcting the causative Fah-splicing mutation and partially restored alpha1-antitrypsin level.