Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Role of rRNA-derived short non-coding RNAs in innate immune response

Award Number: R21AI168975
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/07/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2025

Group Awards By:

View Award Description

Role of rRNA-derived short non-coding RNAs in innate immune response - Project Summary and Abstract Infection of microbes causes a wide range of symptoms and diseases. Sustained efforts to understand the mechanism of cellular defense systems against microbe infections are essential to develop effective prevention methods and therapeutic applications. The innate immune system deploys various pattern-recognition receptors, including Toll-like receptors (TLRs), to recognize the invasion of microbes and initiate protective responses. TLRs are expressed at the cell surface or intracellular compartments (e.g., endosome and lysosome) in various cell types, such as macrophages, and recognize pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) and peptidoglycan (PGN). The PAMP recognition initiates signal transduction pathways that culminate in the activation of transcription factors such as NF-B, resulting in production of cytokines and chemokines to protect the host. Following transcriptional regulation, the downstream of TLR pathways involves regulation at multiple levels including post-transcription steps. In this context, short non- coding RNAs (ncRNAs) have evolved as key post-transcriptional regulators. Among various short ncRNA species, those from ribosomal RNAs (rRNAs), termed rRNA fragments (rRFs), are the most abundant class of short ncRNAs and have recently gained increasing attentions on their expression and functional significance. rRFs are constitutively expressed in multiple organisms including humans, and their expression is involved in regulation of cell cycle and proliferation, apoptosis, and lipid and glucose metabolism. In humans, their expression is modulated in a sex- and population-specific manner, and associated with type 2 diabetes and other diseases. We propose that rRFs play important roles in innate immune response. In preliminary studies, we found that the expression of rRFs is upregulated by the activation of surface TLR in human monocyte-derived macrophages (HMDMs). Importantly, short ncRNA sequencing data demonstrated the abundant accumulation of the rRFs not only in HMDMs but also in their secreted extracellular vehicles (EVs). Further experiments showed that a specific extracellular rRF activates endosomal TLR in the recipient HMDMs to induce cytokine secretion, suggesting that rRFs are not just accumulated as degradation by-products of rRNAs, but are accumulated as functional molecules promoting immune response. In the proposed studies, we will identify the expression profiles of TLR pathway-induced rRFs in HMDMs and their EVs (Aim 1). We will further elucidate the molecular function of extracellular rRFs in endosomal TLR activation (Aim 2). Finally, we will characterize the rRF expression in plasma samples from healthy subjects and patients infected with Mycobacterium tuberculosis (Aim 3). By defining a novel class of TLR pathway-induced rRFs and further establishing their roles, our study will reveal a novel rRNA-engaged ncRNA pathway in the innate immune response and may support the future exploration of biomarkers and efficacious therapeutic applications targeting ncRNAs upon microbe infection.


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 = $0 )
2025	2023	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	2	6/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $195,000 )
2023	2023	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	2	1/23/2023	NON-COMPETING CONTINUATION	$195,000
														Subtotal = $195,000

Issue Date FY: 2022 ( Subtotal = $234,000 )
2022	2022	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	1	2/7/2022	NEW	$234,000
														Subtotal = $234,000

Grand Total All Awards = $429,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of rRNA-derived short non-coding RNAs in innate immune response

Award Number: R21AI168975

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/07/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer