Role of PCIF1 in regulating host-HIV interactions

Ended Project Grant Awarded Last action

Award ID
R56AI187411
Recipient
Awarding agency
Obligated
$502,861

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date
Originally
Place of performance
La Jolla, CA 92093, USA

Award details come from USAspending.gov.

Description

Abstract
RNA modification is an emerging concept because a diverse set of modified nucleotides are found in mrna sequences. The M6A modification is catalyzed by RNA methyltransferase complex containing METTL3 that catalyzes the addition of a methyl group at N6 position of adenosine which affects gene expression via regulation of RNA metabolism, function, and localization. N6,2'-o-dimethyladenosine (M6AM) is an abundant RNA modification located adjacent to the 5'-end of mrna 7-methylguanosine (M7G) cap structure. Since M6AM is found at the first transcribed nucleotide in ~30% of the cellular mrnas, M6AM can have a major influence on gene expression of the transcriptome. Human phosphorylated CTD interacting factor 1 (PCIF1) as cap-specific adenosine-N6-mtase (capam), that catalyzes cap-specific M6A methylation on 2'-o- methylated a at the 5'-ends of mrnas. So far, the role of M6AM RNA modification and the catalytic function of PCIF1 in biological and disease processes, especially in regulating viral infections and host-pathogens interactions have not be determined. Despite remarkable success in treating HIV/aids, we do not have a functional or complete cure for the disease. The molecular networks of host cell regulating HIV-1 transcription, replication, and latency are not completely understood. The overall objective of this proposal is to delineate the molecular and cellular mechanisms by which HIV-1 (HIV) infection alters host transcriptional and translational programs. Our project has three specific aims: aim 1: define the dynamics and mapping of human M6AM RNA methylome by HIV infection and methamphetamine (MA) exposure. Aim 2: determine how HIV alters M6AM methylome of host cell. Aim 3: determine how RNA modifications influences HIV pathogenesis. Successful completion of these aims will reveal function of PCIF1, and a new regulatory mechanism involved in HIV gene expression and latency.

Transactions

Action Obligated Date
Amendment $0
Original award $502,861

Quick answers

Who received award R56AI187411?

R56AI187411 was awarded to University Of California, San Diego by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 24, 2024.

How much is award R56AI187411 worth?

$502,861 has been obligated on R56AI187411.

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