# Epitranscriptomic regulation of spermatogenesis and male fertility

> **NIH NIH R01** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 2020 · $383,709

## Abstract

Project Summary
Reversible chemical modifications of mRNAs have recently been recognized as a major regulatory
mechanism of gene expression. Among >100 various RAN chemical modifications identified so far, N6-
methyladenosine (m6A) represents the most abundant one with ~3-5 m6A sites per mRNA in eukaryotic
transcriptomes. Our recent work (PNAS, 2017, 115:E325) has demonstrated that ALKBH5 acts as a
m6A eraser, and m6A serves as a signal for alternative splicing in the nucleus of spermatocytes and
round spermatids, and for degradation in the cytoplasm of elongating and elongated spermatids. The
scientific premise that proper epitranscriptomic regulation (e.g., m6A) is essential for successful
spermatogenesis and male fertility prompted us to embark on investigations aiming to understand
how m6A levels are controlled in developing male germ cells and what role this specific chemical
modification of mRNA plays in the regulation of spermatogenesis. Based upon our published and
preliminary data, we hypothesize that ALKBH4, a homolog of ALKBH5, regulates mRNA m6A levels in
spermatogenic cells either as a novel eraser or a co-factor of ALKBH5. To test this hypothesis, we will
first determine whether ALKBH4 functions as a novel RNA m6A demethylase or as a co-factor for
ALKBH5 using biochemical analyses in vitro (Aim1). The in vitro findings will then be validated using
knockout mouse models in vivo and the physiological role of ALKBH4 in the regulation of
spermatogenesis will also be determined (Aim2). The proposed project will help us gain insights into the
epitranscriptomic regulation of spermatogenesis and the knowledge gained would help us discover the
underlying causes of poor sperm quality and male infertility.

## Key facts

- **NIH application ID:** 9941546
- **Project number:** 1R01HD099924-01A1
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **Principal Investigator:** Wei Yan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,709
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941546

## Citation

> US National Institutes of Health, RePORTER application 9941546, Epitranscriptomic regulation of spermatogenesis and male fertility (1R01HD099924-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9941546. Licensed CC0.

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