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Role of microtubules in the non-cell autonomous activities of plant microRNAs

Award Number: R01GM129373
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/05/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Role of microtubules in the non-cell autonomous activities of plant microRNAs - PROJECT SUMMARY microRNAs (miRNAs) are sequence-specific regulators of gene expression that impact almost all biological processes in diverse eukaryotes. Defects in miRNA-based regulation lead to developmental and physiological abnormalities in both plants and animals. Thanks to nearly two decades of research, the molecular machinery responsible for miRNA biogenesis and modes of action has been uncovered. However, since most biochemical studies on miRNAs or related small interfering RNAs were performed with cell-free extracts, how the small RNA machinery interplays with the cytoskeleton remains largely unknown. Historically, miRNAs are viewed as cell-autonomous regulatory molecules, but in recent years, mounting evidence points to the existence of miRNAs in extracellular vesicles in animals as well as the movement of miRNAs between cells in plants. Despite accumulating evidence implicating miRNAs as informational molecules in cell-cell communications, the scope of biologically significant, non-cell autonomous activities of miRNAs is largely unknown, let alone the molecular mechanisms that enable, constrain, or regulate the non-cell autonomy of miRNAs. The project interrogates the scope of miRNAs serving as informational molecules in cell-cell communications and investigates the mechanisms underlying the non-cell autonomous activities of miRNAs using the Arabidopsis model. In addition to sophisticated tool sets as available resources, advantages offered by the Arabidopsis model include the well-documented, non-cell autonomous activities of a few miRNAs in intact plants and the ease to perform forward genetic screens that do not require any a priori assumptions regarding the cellular machinery for miRNA’s non-cell autonomy. A forward genetic screen from the PI’s group revealed a previously unsuspected link between microtubules and the non-cell autonomous activities of miRNAs as well as a tantalizing connection between the translation repression activities of miRNAs and their non-cell autonomous activities. The project takes advantage of the layered cell organization in roots and employs genomics approaches at single-cell-layer resolution to study how microtubules enable the non-cell autonomous activities of miRNAs. By elucidating the scope of miRNA’s non-cell autonomy, the project has the potential to change the dogma that miRNAs largely act cell-autonomously and set the paradigm that miRNAs serve as signals in cell- cell communications. Through pioneering efforts to interrogate mechanisms underlying the non-cell autonomous activities of miRNAs, the project will provide initial knowledge in this largely unknown territory and set the foundation for future studies. By revealing a role of the cytoskeleton in small RNA biology, the impacts of the project will reach beyond plant biology.


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: 2024 ( Subtotal = $0 )
2024	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Biomedical Research and Research Training	000	4	1/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $311,000 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Biomedical Research and Research Training	000	4	7/30/2021	NON-COMPETING CONTINUATION	$311,000
														Subtotal = $311,000

Issue Date FY: 2020 ( Subtotal = $311,000 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Biomedical Research and Research Training	000	3	8/12/2020	NON-COMPETING CONTINUATION	$311,000
														Subtotal = $311,000

Issue Date FY: 2019 ( Subtotal = $311,000 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Biomedical Research and Research Training	000	2	8/15/2019	NON-COMPETING CONTINUATION	$311,000
														Subtotal = $311,000

Issue Date FY: 2018 ( Subtotal = $311,000 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Biomedical Research and Research Training	000	1	9/5/2018	NEW	$311,000
														Subtotal = $311,000

Grand Total All Awards = $1,244,000

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Role of microtubules in the non-cell autonomous activities of plant microRNAs

Award Number: R01GM129373

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/05/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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