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Role of ROP GTPases in sulfate transceptor SULTR1;2-regulated sulfur nutrient sensing

Award Number: R16GM145531
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: 07/15/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Role of ROP GTPases in sulfate transceptor SULTR1;2-regulated sulfur nutrient sensing - ABSTRACT Many living organisms including humans have evolved mechanisms to sense and respond to levels of mineral nutrients or amino acids. In this application, we propose to use Arabidopsis plant sulfur (S) nutrient sensing and signaling as an experimental system to dissect transporting receptor-mediated nutrient sensing mechanisms. Our prior research has led to identification of sulfate transporter SULTR1;2 as a receptor. This type of dual-function transporting receptor, termed transceptor, has been increasingly found in eukaryotic organisms and is expected to increase nutrient use efficiency by performing both its sensing and transporting functions. However, how plants use the transceptor SULTR1;2 to transduce the S signal in the control of gene expression has remained a central unanswered question and becomes the focus of the present project. Our recent studies have revealed a conserved shortcut model of transcriptional control that links Rho family small GTPases to RNA polymerase II (Pol II) C-terminal domain (CTD) Ser phosphorylation across plants, fungi and humans. The Pol II CTD contains various number of conserved heptad peptide repeats (Y1S2P3T4S5P6S7) in which each amino acid can be subjected to different posttranslational modifications. Thus, the posttranslational modification pattern is complex and collectively called the CTD code. Among the CTD code, Ser2 and Ser5 phosphorylation along the gene is very important for initiating transcription and completing the transcription cycle. In the classical model of transcriptional control, upon activation by Rho or Ras GTPases, the MAP kinase cascade activates transcription factors that bind to gene-specific cis-elements and helps recruit Pol II to the core promoter. In contrast, in the shortcut model, Rho GTPase signaling directly targets the Pol II CTD Ser2 and Ser5 phosphorylation and thus can rapidly bring about large-scale gene expression changes. We now have preliminary evidence indicating that activity of ROP2 GTPase, which is a member of plant-unique ROP subfamily of Rho GTPases, and levels of CTD Ser2 and Ser5 phosphorylation are impacted by S status. In addition, ROP GTPase activity is higher in SULTR1;2 mutants. Therefore, we hypothesize that ROP2 and its functionally redundant ROP4 act as negative regulators in SULTR1;2-mediated S sensing and signaling. The proposed work aims to fill the major gaps from SULTR1;2 to Pol II transcription. Specifically, Aim 1 is to test that ROP2 and ROP4 GTPases act as negative regulators in SULTR1;2-mediated S sensing and signaling using genetic and biochemical approaches. Aim 2 is to test the hypothesis that ROP2-mediated Pol II shortcut model is required for S response. In Aim 3, we propose to test that ROP2-controlled SLIM1 transcription factor activity and ROP2-mediated Pol II CTD code modulation act cooperatively to achieve the most productive transcription of S-deficiency induced S-response genes. The proposed study will not only lead to novel mechanistic insights into how plants use nutrient transceptor SULTR1;2 and ROP signaling switch to efficiently control gene expression but also provide a paradigm for transcriptional regulation in other organisms.


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: 2025 ( Subtotal = $146,077 )
2025	2025	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	250 BEDFORD PARK BLVD W	BRONX	NY	10468	BRONX	USA	Biomedical Research and Research Training	000	4	6/23/2025	NON-COMPETING CONTINUATION	$146,077
														Subtotal = $146,077

Issue Date FY: 2024 ( Subtotal = $145,298 )
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	250 BEDFORD PARK BLVD W	BRONX	NY	10468	BRONX	USA	Biomedical Research and Research Training	000	3	5/22/2024	NON-COMPETING CONTINUATION	$145,298
														Subtotal = $145,298

Issue Date FY: 2023 ( Subtotal = $145,114 )
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	250 BEDFORD PARK BLVD	BRONX	NY	10468	BRONX	USA	Biomedical Research and Research Training	000	2	6/14/2023	NON-COMPETING CONTINUATION	$145,114
														Subtotal = $145,114

Issue Date FY: 2022 ( Subtotal = $145,418 )
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	250 BEDFORD PARK BLVD	BRONX	NY	10468	BRONX	USA	Biomedical Research and Research Training	000	1	7/15/2022	NEW	$145,418
														Subtotal = $145,418

Grand Total All Awards = $581,907

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Role of ROP GTPases in sulfate transceptor SULTR1;2-regulated sulfur nutrient sensing

Award Number: R16GM145531

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: 07/15/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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