Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology > Dipali Sashital

Dipali Sashital

Assistant Professor

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  • Structure, function and assembly of RNA-protein complexes

3252 Molecular Biology Building
Dept. of Biochemistry, Biophysics & Molecular Biology
Iowa State University
Ames, IA  50011

Phone:  (515) 294-5121
E-mail:  sashital@iastate.edu


Sashital Laboratory Website:   www.sashitallab.org


Education

B.S., Chemistry and Biochemistry, University of Michigan, Ann Arbor, 2001
Ph.D., Biochemistry, University of Wisconsin, Madison, 2006
Postdoctoral Fellow, University of California, Berkeley, 2008-2011
Postdoctoral Fellow, The Scripps Research Institute, 2012-2013


Research Interests

RNA-protein (RNP) complexes are central to many fundamental processes of gene regulation and genome maintenance in all kingdoms of life.  The RNA components of these molecular machines often carry out diverse functions, acting as guide, template, scaffold, or catalyst.  Despite this versatility, RNAs require protein partners to function, and the interactions that form between these components often dictate the overall activity of the RNP complex.  Our lab is interested in understanding the molecular mechanisms underlying the function of RNPs from diverse cellular pathways.  To that end, we combine a broad range of biochemical and structural tools to study RNA and protein structure, interactions and function.

In particular, we are interested in RNA-protein complexes involved in bacterial and archaeal CRISPR (clustered regularly interspaced short palindromic repeats) immune systems.  These interference pathways utilize small guide RNAs that partner with effector proteins to neutralize foreign genetic threats from bacteriophage and plasmids.  CRISPR RNPs must survey the complex milieu of the cell for invasive nucleic acids, targeting them for destruction while avoiding potentially damaging off-target effects.  Our lab hopes to understand both the molecular details of this interference mechanism and the activation of CRISPR systems during immune response.


Recent Publications

1:  Sashital DG, Wiedenheft B, Doudna JA. Mechanism of foreign DNA selection in a bacterial adaptive immune system. Mol Cell. 2012 Jun 8;46(5):606-15. doi: 10.1016/j.molcel.2012.03.020. Epub 2012 Apr 19. PubMed PMID: 22521690; PubMedCentral PMCID: PMC3397241.

2:  Burke JE, Sashital DG, Zuo X, Wang YX, Butcher SE. Structure of the yeast U2/U6 snRNA complex. RNA. 2012 Apr;18(4):673-83. doi: 10.1261/rna.031138.111. Epub 2012 Feb 10. PubMed PMID: 22328579; PubMed Central PMCID: PMC3312555.

3:  Sashital DG, Jinek M, Doudna JA. An RNA-induced conformational change required for CRISPR RNA cleavage by the endoribonuclease Cse3. Nat Struct Mol Biol. 2011 Jun;18 6):680-7. doi: 10.1038/nsmb.2043. Epub 2011 May 15. PubMed PMID: 21572442.

4:  Sashital DG, Doudna JA. Structural insights into RNA interference. Curr Opin Struct Biol. 2010 Feb;20(1):90-7. doi: 10.1016/j.sbi.2009.12.001. Epub 2010 Jan 5. Review. PubMed PMID: 20053548; PubMed Central PMCID: PMC2855239.

5:  Sashital DG, Venditti V, Angers CG, Cornilescu G, Butcher SE. Structure and thermodynamics of a conserved U2 snRNA domain from yeast and human. RNA. 2007 Mar;13(3):328-38. Epub 2007 Jan 22. PubMed PMID: 17242306; PubMed Central PMCID: PMC1800520.

6:  Sashital DG, Butcher SE. Flipping off the riboswitch: RNA structures that control gene expression. ACS Chem Biol. 2006 Jul 21;1(6):341-5. Review. PubMed PMID: 17163768.

7:  Sashital DG, Cornilescu G, McManus CJ, Brow DA, Butcher SE. U2-U6 RNA folding reveals a group II intron-like domain and a four-helix junction. Nat Struct Mol Biol. 2004 Dec;11(12):1237-42. Epub 2004 Nov 14. Erratum in: Nat Struct Mol Biol. 2005 Jan;12(1):99. PubMed PMID: 15543154.

8:  Sigel RK, Sashital DG, Abramovitz DL, Palmer AG, Butcher SE, Pyle AM. Solution structure of domain 5 of a group II intron ribozyme reveals a new RNA motif. Nat Struct Mol Biol. 2004 Feb;11(2):187-92. Epub 2004 Jan 25. PubMed PMID: 14745440.

9:  Sashital DG, Allmann AM, Van Doren SR, Butcher SE. Structural basis for a lethal mutation in U6 RNA. Biochemistry. 2003 Feb 18;42(6):1470-7. PubMed PMID:12578359; PubMed Central PMCID: PMC3124365.

 

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