New classes of animal small silencing RNAs

Organizer: Philip Zamore, U. Massachusetts Medical Center

Abstracts

Alexei Aravin, Cold Spring Harbor Laboratories:
"Piwi proteins and associated small RNAs in germline development"

Argonaute proteins and associated small RNAs have critical role in development by regulating messenger RNA stability, protein synthesis, chromatin organization and genome structure. In animals, Argonaute proteins segregate into two subfamilies. Ubiquitously expressed members of Argonaute subfamily bind 21-23 nt RNA and act in RNA interference and in microRNA-mediated gene regulation. The Piwi subfamily is involved in germline-specific events such as germline stem cell maintenance and meiosis. Particularly, three members of the Piwi subfamily in mouse are critical for successful spermatogenesis. Recently we identified a new class of 25-30 nt RNAs (piRNAs) as a binding partner of Piwi proteins in the mammalian male germ cells. piRNAs are highly abundant in germ cells and accumulate at the onset of meiosis. Thousands of identified piRNAs show distinctive localization patterns in the genome, being predominantly grouped into 20-90-kilobase clusters scattered throughout genome. We explore biogenesis of piRNAs and function of Piwi-piRNA complexes in the mammalian and Drosophila germline.

Nelson Lau, Harvard Medical School:
"The Piwi-interacting RNA Complex from Rat Testis"

Animals utilize numerous small interfering RNAs and microRNAs to control gene expression by regulating messenger RNAs. Joining these prototypical gene regulators is a novel class of small RNAs that are expressed predominantly in the male germline and interact with Piwi family proteins. We have purified and analyzed Piwi-interacting RNAs (piRNAs) and the native piRNA complex (piRC) from rat testis. piRC components exhibit characteristics and activities that suggest a role in gene silencing, and sequence analyses indicate a novel genomic configuration for these non-coding RNAs. The features of piRC distinguish it from other small RNA complexes and suggest a new dimension to RNA gene silencing in animals.

Doron Betel, Robert Sheridan, Chris Sander; Computational Biology Center, Memorial Sloan-Kettering Cancer Center:
"Computational analysis of piRNA datasets"

A recent landmark discovery has identified a novel class of small RNA in mammalian testes that is expressed during spermatogenesis. Members of this class termed PIWI-interacting RNA (piRNA) are typically ~30 base long, interact with PIWI proteins and are organized into distinct genomic clusters. The homology of PIWI to Argonaute proteins, key components of the interfering RNA pathway, suggests a role in RNA-dependent regulatory processes during meiosis. We have conducted a detailed comparison of sequences and cluster organization of the available comprehensive mouse piRNA datasets. We report the results of our comparisons and discuss their implications in terms of piRNA biogenesis.