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A Deeper Silence: Piwi-Interacting RNA (piRNA) and the Genome

A Deeper Silence
Reported by
Angelo DePalma

Posted April 09, 2007


Piwi-interacting RNA (piRNA)—a major class of small regulatory RNA—was discovered by four labs more or less simultaneously in 2006. PiRNAs have a distinct size, 26 to 30 nucleotides, and originate from a rather narrow range of genetic locations, or loci. These regulatory RNAs have been detected in both egg- and sperm-producing cells in fruit flies, but are only found in sperm-producing cells in mammals. They are associated with specialized proteins from the Argonaute family, the "Piwi" proteins, from which piRNAs are named. Argonaute proteins catalyze some of the chemical operations required for gene silencing in both microRNAs and siRNAs, and are expected to behave similarly in piRNAs. At the December 5, 2006, meeting of the RNAi Discussion Group, the topics discussed ranged from the identification of piRNAs to attempts to determine their biogenesis, abundance, and their function within germ cells.

Use the tabs above to find a meeting report and multimedia from this event.

Piwi Proteins and Associated Small RNAs in Germline Development

Altuvia Y, Landgraf P, Lithwick G, et al. 2005. Clustering and conservation patterns of human microRNAs. Nucleic Acids Res. 33: 2697-2706. Full Text

Aravin A, Gaidatzis D, Pfeffer S, et al. 2006. A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442: 203-207.

Aravin A, Tuschl T. 2005. Identification and characterization of small RNAs involved in RNA silencing. FEBS Lett. 579: 5830-5840.

John B, Enright AJ, Aravin A, et al. 2004. Human MicroRNA targets. PLoS Biol. 2: e363. Full Text

Sewer A, Paul N, Landgraf P, et al. 2005. Identification of clustered microRNAs using an ab initio prediction method. BMC Bioinformatics 6: 267. Full Text

The Piwi-interacting RNA Complex from Rat Testis

Abbott AL, Alvarez-Saavedra E, Miska EA, et al. 2005. The let-7 MicroRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans. Dev. Cell 9: 403-414.

Lau NC, Lai EC. 2005. Diverse roles for RNA in gene regulation. Genome Biol. 6: 315.

Lau NC, Seto AG, Kim J, et al. 2006. Characterization of the piRNA complex from rat testes. Science 313: 363-367.

Li M, Jones-Rhoades MW, Lau NC, et al. 2005. Regulatory mutations of mir-48, a C. elegans let-7 family MicroRNA, cause developmental timing defects. Dev. Cell 9: 415-422.

Lim LP, Lau NC, Garrett-Engele P, et al. 2005. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433: 769-773.

Ancient Pathways Programmed by Small RNA

Matranga C, Tomari Y, Shin C, et al. 2005. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123: 607-620.

Schwarz DS, Ding H, Kennington L, et al. 2006. Designing siRNA that distinguish between genes that differ by a single nucleotide. PLoS Genet. 2: e140. Full Text

Seitz H, Zamore PD. 2006. Rethinking the microprocessor. Cell 125: 827-829.

Vagin VV, Sigova A, Li C, et al. 2006. A distinct small RNA pathway silences selfish genetic elements in the germline. Science 313: 320-324.

Zamore PD. 2006. RNA interference: big applause for silencing in Stockholm. Cell 127: 1083-1086.


Alexei Aravin, PhD

Cold Spring Harbor Laboratory
e-mail | publications

Alexei Aravin is a postdoctoral fellow in the laboratory of Greg Hannon at Cold Spring Harbor Laboratory. He is working on a long-term project to understand the function and molecular mechanism of the small RNA pathway in the germline. Aravin obtained his PhD from the Institute of Molecular Genetics at the Russian Academy of Sciences in Moscow. His thesis work was on the regulation of expression of the heterochromatic Stellate genes in Drosophila melanogaster. After completing his PhD, Aravin did postdoctoral work in the laboratory of Thomas Tuschl at Rockefeller University before moving to Hannon's lab at Cold Spring Harbor.

Nelson C. Lau, PhD

Harvard Medical School
e-mail | web site | publications

Nelson Lau is a postdoctoral fellow in the laboratory of Robert Kingston at Massachusetts General Hospital and Harvard Medical School. Along with Anita Seto, he discovered the class of germ-line specific RNAs called Piwi-interacting RNAs and the piRNA complex from rats. He is characterizing the biochemical properties of the piRNA complex and the genomic characteristics of mammalian piRNAs. Lau obtained his PhD from Massachusetts Institute of Technology and the Whitehead Institute. For his thesis, he developed a cloning method that isolated microRNAs from C. elegans, and characterized the sequences, developmental expression patterns, and molecular abundance of the microRNAs. He also constructed inducible microRNA-expressing cell lines for determination of microRNAs stability.

Doron Betel, PhD

Memorial Sloan-Kettering Cancer Center
e-mail | web site | publications

Doron Betel is a postdoctoral fellow with Chris Sander at the Memorial Sloan-Kettering Cancer Center in New York. His research interest is in applying computational methods to the study of small regulatory RNAs. Specific areas of interest include studying the function of the newly discovered testes-specific small RNAs termed piRNAs, microRNA target prediction, the role of microRNAs in stem cell development and the evolution of microRNAs. Betel received his PhD from the University of Toronto where he undertook a computational study of the role of conserved domains in protein interactions for his thesis work.

Phillip D. Zamore, PhD

University of Massachusetts Medical School
e-mail | web site | publications

Phillip D. Zamore is the Gretchen Stone Cook Professor of Biomedical Sciences at University of Massachusetts Medical School. Zamore received his AB in 1986 and his PhD in 1992 from the Department of Biochemistry and Molecular Biology at Harvard University. He received a Life Sciences Research Foundation and a Charles H. Hood Fellowship to do postdoctoral work at the Whitehead Institute at the Massachusetts Institute of Technology. He joined the Department of Biochemistry and Molecular Biology at the University of Massachusetts Medical School as a faculty member in November 1999 and is a 2000 Pew Scholar in the Biomedical Sciences. In 2002, he became a W.M. Keck Foundation Young Scholar in Medical Research.

Angelo DePalma


Angelo DePalma is a freelance writer based in Newton, New Jersey. In 1984, he received a PhD in chemistry from the State University of New York, Stony Brook. His work appears in a dozen pharmaceutical industry trade magazines, and he is the author of a bestselling book on vitamins and supplements.