RNA polymerase II transcripts (heterogeneous nuclear RNA) are associated with nuclear ribonucleoprotein particles (hnRNP). These particles may have a central role in mRNA processing. In this application, we seek continued support for a program on hnRNP structure and function. The proposed experiments make use exclusively of specific gene transcripts, rather than total hnRNP. These studies involve in vitro transcription of cloned genes by RNA polymerase II, combined with our recent successful in vitro assembly of specific hnRNP particles. The research also exploits new techniques we have developed for probing RNA-protein and RNA-RNA interactions. Three main lines of investigation will be pursued regarding hnRNP function: (1) Do hnRNP proteins have specific DNA-binding properties?, (2) does the nascent transcript interact with the template and do hnRNP proteins attenuate this process?, and (3) is hnRNP structure important for splicing? hnRNP structure will be studied with emphasis on sequence-specific aspects, as well as vicinal interactions of small nuclear RNA-associated proteins with the hnRNA strand.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM021595-11
Application #
3270594
Study Section
Molecular Biology Study Section (MBY)
Project Start
1977-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Worcester Foundation for Biomedical Research
Department
Type
DUNS #
City
Shrewsbury
State
MA
Country
United States
Zip Code
Pederson, Thoru; King, Megan C; Marko, John F (2015) Forces, fluctuations, and self-organization in the nucleus. Mol Biol Cell 26:3915-9
Pederson, Thoru (2011) The nucleus introduced. Cold Spring Harb Perspect Biol 3:
Pederson, Thoru (2011) The nucleolus. Cold Spring Harb Perspect Biol 3:
Pederson, Thoru; Tsai, Robert Y L (2009) In search of nonribosomal nucleolar protein function and regulation. J Cell Biol 184:771-6
Pederson, Thoru (2009) The discovery of eukaryotic genome design and its forgotten corollary--the postulate of gene regulation by nuclear RNA. FASEB J 23:2019-21
Rulli Jr, Samuel J; Hibbert, Catherine S; Mirro, Jane et al. (2007) Selective and nonselective packaging of cellular RNAs in retrovirus particles. J Virol 81:6623-31
Pederson, Thoru (2007) Ribosomal protein mutations in Diamond-Blackfan anemia: might they operate upstream from protein synthesis? FASEB J 21:3442-5
Sommerville, John; Brumwell, Craig L; Politz, Joan C Ritland et al. (2005) Signal recognition particle assembly in relation to the function of amplified nucleoli of Xenopus oocytes. J Cell Sci 118:1299-307
Pederson, Thoru (2004) RNA interference and mRNA silencing, 2004: how far will they reach? Mol Biol Cell 15:407-10
Pederson, Thoru (2004) Can telomerase be put in its place? J Cell Biol 164:637-9

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