Small regulatory RNAs (and their associated proteins) are dynamic and active participants in controlling the genome and phenotype of cells and animals. Germ cells have a special role in the perpetuation of organisms, but they have also become the richest environment for the study of small regulatory RNAs. In addition to microRNAs, which are vital regulators conserved from plants to people, germ cells express endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs). In animal germ cells, like spermatocytes and oocytes, piRNAs are the most abundant class of small RNAs, and together with Piwi proteins, they suppress the mobilization of transposable elements and specify the organization of mRNAs and proteins in the germ cell, which impacts the expression of certain genes
Our group is interested in dissecting the molecular mechanisms of Piwi proteins and piRNAs, with a focus on particular outstanding questions. How exactly do Piwi proteins and piRNAs silence transposons and organize asymmetrically in germ cells? What is the impact of these molecules on global gene expression and chromatin organization and how does this affect germ cell and embryonic development? How do piRNAs get generated and what triggers their specific expression in germ cells? We hope to address these questions with molecular, cell biology, and biochemical approaches in specific model systems, like Xenopus oocytes, a repository and "living test tube" of Piwi proteins and piRNAs. Insights we gain from piRNA studies will complement our examinations of other RNAi pathways, like microRNAs and endo-siRNAs.
Rahman, R, Chirn,GW, Kanodia, A, Sytnikova, YA, Brembs, B, Bergman, CM, and Lau, NC. Unique transposon landscapes are pervasive across Drosophila melanogaster genomes. Under Review.
Chirn,GW, Rahman, R, Sytnikova, YA, Matts, JA, Zeng, M, Gerlach, D, Yu, M, Berger, B, Kile, BT, and Lau, NC. Conserved piRNA expression from a distinct set of piRNA cluster loci in Eutherian mammals. Under Review.
Sytnikova, YA., Rahman, R., Chirn, G.W., Post, C., Clark, J., and Lau, N.C. (2014). Transposable element dynamics and PIWI regulation impacts lncRNA and gene expression diversity in Drosophila ovarian cell cultures. Genome Res. Dec;24(12):1977-90. Additional items for this paper.
Post, C, Clark, JP, Sytnikova, Y., Chirn, G.W., and Lau, N.C. (2014). The capacity of target silencing by the Drosophila Piwi protein and piRNAs. RNA. Dec;20(12):1977-86.
Clark, JP, and Lau, N.C. (2014) Piwi proteins and piRNAs step onto the systems biology stage. Adv Exp Med Biol. Systems Biology and Genomics of RNA binding proteins and RNA processing. 2014;825:159-97. doi: 10.1007/978-1-4939-1221-6_5.
Ow MC, Lau NC, Hall SE. (2014) Small RNA Library Cloning Procedure for Deep Sequencing of Specific Endogenous siRNA Classes in Caenorhabditis elegans. Methods Mol Biol.1173:59-70. doi: 10.1007/978-1-4939-0931-5_6.
Arnold CD, Gerlach D, Spies D, Matts JA,Sytnikova YA, Pagani M, Lau NC, Stark A. (2014). Quantitative genome-wide enhancer activity maps in five Drosophila species reveal the extent of functional enhancer conservation and turnover during cis-regulatory evolution. Nature Genetics, 2014 Jul;46(7):685-92.
Ghiretti AE, Moore AR, Brenner RG, Chen LF, West AE, Lau NC, Van Hooser SD, Paradis S. (2014) Rem2 is an activity-dependent negative regulator of dendritic complexity in vivo. J Neurosci. Jan 8;34(2):392-407. PMID: 24403140 PMCID: PMC3870928.
Matts, J.A., Sytnikova, Y., Chirn, G., Igloi, G.L., and Lau, N.C. (2014). Small RNA library construction from minute biological samples. Methods in Molecular Biology. Ed. M. Siomi. 1093:123-36.
Zeng, M., Kuzirian M.S., Harper, L., Paradis, S., and Lau, N.C. (2013). Organic small hairpin RNAs (OshR): a Do-It-Yourself platform for transgene-based gene silencing. Methods. 2013 May 23. pii: S1046-2023(13)00148-5. doi: 10.1016/j.ymeth.2013.05.007.
Sytnikova, Y, and Lau, N.C. (2013). Does the APC/C mark MIWI and piRNAs for a final farewell? Developmental Cell. Jan 28;24(2):119-20.
Hall, S.E., Chirn, G.W., Lau, N.C. and Sengupta, P. (2013). RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans. RNA. Mar;19(3):306-19.
Lau NC. Guiding and guarding gonads: animal germline small RNAs. Int J Biochem Cell Biol. 2010. Aug;42(8):1334-47. Epub 2010 Mar 19.
Robine N*, Lau NC*†, Balla S*, Jin Z, Okamura K, Kuramochi-Miyagawa S, Blower MD, Lai EC. A broadly conserved pathway generates 3' UTR-directed primary piRNAs. Curr Biology. 2009. Dec 29;19(24):2066-76.
Lau NC*†, Robine N*, Martin R, Chung WJ, Niki Y, Berezikov E, Lai EC. Abundant primary piRNAs, endo-siRNAs and microRNAs in a Drosophila ovary cell line. Genome Research. 2009. Oct;19(10):1776-85.
Lau NC, Ohsumi T, Borowsky ML, Kingston RE, Blower MD. Systematic and single cell analysis of Xenopus Piwi-interacting RNAs and Xiwi. EMBO Journal. 2009. Oct 7;28(19):2945-58.
Lau NC. Analysis of small endogenous RNAs. Curr Protoc Mol Biol. 2008 Jan; Chapter 26:Unit26.7.
Seto AG*, Kingston RE, Lau NC*. The coming of age for Piwi proteins. Mol Cell. 2007 Jun 8;26(5):603-9. [PDF].
Lau NC*, Seto AG*, Kim J, Kuramochi-Miyagawa S, Nakano T, Bartel DP, Kingston RE. Characterization of the piRNA complex from rat testes. Science. 2006 Jul 21;313(5785):363-7. Epub 2006 Jun 15.
Lau NC, Lai EC. Diverse roles for RNA in gene regulation. Genome Biol. 2005;6(4):315. Epub 2005 Mar 29.
Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005 Feb 17;433(7027):769-73. Epub 2005 Jan 30.
Lim LP*, Lau NC*, Weinstein EG*, Abdelhakim AH*, Yekta SO, Rhoades MW, Burge CB, Bartel DP. The MicroRNAs of Caenorhabditis elegans. Genes Dev. 2003 Apr 15;17(8):991-1008. Epub 2003 Apr 02.
Lau NC, Bartel DP. Censors of the Genome. Scientific American. 2003 Aug;289(2):34-42.
Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 2001 Oct 26;294(5543):858-62
Small RNA Library Construction for Illumina GAII platform.
Quick Q-column Chromatography Isolation of Argonaute and Piwi Complexes.
* equal contributors
Last update: September 30, 2015