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Trans-Regulation of RNA-Binding Protein Motifs by MicroRNA

Award Number: R21HG008495
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/18/2015
PERIOD OF PERFORMANCE END DATE: 04/30/2017

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Trans-Regulation of RNA-Binding Protein Motifs by MicroRNA - ¿ DESCRIPTION (provided by applicant): We have discovered that micoRNAs can modulate RNA-binding protein (RBP) binding sites in a dynamic manner and suggest that miRNAs indirectly or directly modulate RBP-binding sites in a dynamic manner adding complexity and hierarchy to a post-transcriptional regulatory code. This model, which we call "sxRNA" for structurally interacting RNA, represents an exciting new post-transcriptional regulatory paradigm that may provide fundamental aspects of gene expression regulation. We have informatically identified several "trans-acting" sxRNAs and our preliminary data suggests that both positive and negative variations are possible. Examples of negative or "repressor" sxRNA complexes inhibit RBP binding activity, while positive or "inducer" versions of sxRNA complexes may increase RBP binding and can be captured using RBP immunoprecipatation (RIP) followed by miRNA analysis. This novel regulatory mechanism may explain how complex regulation of gene multi-functionality including alternative splicing could be regulated at the post-transcriptional level. Furthermore, combinations of these interactions could be used in a modular and combinatorial manner adding a hierarchical complexity to the post-transcriptional regulatory code. Similar to the impressive microRNA field, sxRNA has the potential to increase our understanding of gene regulation while simultaneously creating technological opportunities to utilize this regulation as a tissue specific mRNA alternative to gene therapy, anti-viral, RNA-based molecular tool, diagnostic, or even therapeutic that exploits these newly discovered post-transcriptional approaches. The goal of this proposal is to test a new post-transcriptional model in which miRNA and RBPs compete in trans to influence RNA structure. This project is designed to identify dozens (possibly hundreds) of naturally occurring microRNA-mRNA-RBP interactions by exploiting both experimental and informatic approaches, characterize the structural nature of the sxRNA trans-RNA interaction and its effect on RBP binding and validate their existence and role in translation in a cellular system using a specifically designed MS2-sxRNA reporter.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2017 ( Subtotal = -$3 )
2017	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Human Genome Research	002	3	12/13/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$17,995
2017	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	1400 WASHINGTON AVE	ALBANY	NY	12222	ALBANY	USA	Human Genome Research	001	2	12/13/2016	NON-COMPETING CONTINUATION	-$1,192
2017	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Human Genome Research	003	3	7/31/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$3
2017	2015	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	1400 WASHINGTON AVE	ALBANY	NY	12222	ALBANY	USA	Human Genome Research	000	1	12/13/2016	NEW	-$16,803
														Subtotal = -$3

Issue Date FY: 2016 ( Subtotal = $189,377 )
2016	2016	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Human Genome Research	002	3	9/23/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$188,185
2016	2016	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Human Genome Research	001	2	9/23/2016	NON-COMPETING CONTINUATION	-$188,185
2016	2016	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Human Genome Research	000	2	4/22/2016	NON-COMPETING CONTINUATION	$189,377
														Subtotal = $189,377

Issue Date FY: 2015 ( Subtotal = $227,214 )
2015	2015	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Human Genome Research	000	1	5/16/2015	NEW	$227,214
														Subtotal = $227,214

Grand Total All Awards = $416,588

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Trans-Regulation of RNA-Binding Protein Motifs by MicroRNA

Award Number: R21HG008495

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/18/2015

PERIOD OF PERFORMANCE END DATE: 04/30/2017

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