# Characterization of the mammalian mRNA 3'-end processing complex

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $318,270

## Abstract

Project summary:
The long-term goal of this proposal is to understand, in detail, the mechanisms of
mammalian mRNA 3' processing and its regulation. mRNA 3'-end formation, typically
involving an endonucleolytic cleavage followed by polyadenylation, is an essential step
of eukaryotic gene expression and it significantly impacts many aspects of RNA
metabolism, including mRNA stability, subcellular localization and translation. In
addition, the majority of eukaryotic genes produce multiple mRNA isoforms with distinct
3' ends through alternative polyadenylation (APA). Recent studies have revealed that
APA is highly regulated in development and plays an important role in post-
transcriptional gene regulation. Aberrant APA patterns have been associated with a wide
range of diseases, from cancer to neurological disorders. Two key outstanding
questions in the mRNA 3' processing field have been: 1) what is the molecular
mechanism of mRNA 3' processing (including mechanisms for poly(A) site (PAS)
recognition and catalysis of cleavage and polyadenylation)? 2) how is PAS
selection or APA regulated? To address these fundamental questions, it is essential to
understand the structure-function relationship of mRNA 3' processing factors. In
published studies during the previous funding periods, we have reconstituted key
modules of the mammalian mRNA 3' processing complex, characterized how AAUAAA
and the U/GU-rich downstream element (two key elements that define the majority of
mammalian PAS) are recognized, and revealed that mRNA 3' processing and splicing
can be regulated through a similar mechanism. Building on these findings, here we
propose to define the structure-function relationship of the fully reconstituted human
mRNA 3' processing complex and systematically characterize the role of RNA-binding
proteins (RBPs) in regulating PAS selection and APA.
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## Key facts

- **NIH application ID:** 10135984
- **Project number:** 5R01GM090056-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Yongsheng Shi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $318,270
- **Award type:** 5
- **Project period:** 2010-03-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135984

## Citation

> US National Institutes of Health, RePORTER application 10135984, Characterization of the mammalian mRNA 3'-end processing complex (5R01GM090056-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135984. Licensed CC0.

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