Accession

PRJCA002922

Title

METTL3-mediated m6A modification is required for cerebellar development m6A modification and cerebellar development

Relevance

Medical

Data types

Epigenomics
Transcriptome or Gene expression
Raw sequence reads

Organisms

Mus musculus

Description

N6-methyladenosine (m6A) RNA methylation is the most abundant modification on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex including methyltransferase like 3 (METTL3) as a key factor. However, the in vivo functions of METTL3 and m6A modification in mammalian development remain unclear. Here we show that specific inactivation of Mettl3 in mouse nervous system causes severe developmental defects in the brain. Mettl3 conditional knockout mice manifest cerebellar hypoplasia caused by drastically enhanced apoptosis of new born cerebellar granule cells (CGCs) in the external granular layer (EGL). METTL3 depletion induced loss of m6A modification causes extended RNA half-lives and aberrant splicing events, consequently leading to dysregulation of transcriptome-wide gene expression and premature CGC death. Our findings reveal a critical role of METTL3-mediated m6A in regulating the development of mammalian cerebellum.

Sample scope

Multiisolate

Release date

2020-06-25

Publication

PubMed ID	Article title	Journal name	DOI	Year
29879109

Biomaterial provider

Beijing Institute of Genomics, Yungui Yang Lab; nstitute of Zoology, Chinese Academy of Sciences, Qi Zhou Lab

Grants

Agency	program	Grant ID	Grant title
National Natural Science Foundation of China (NSFC)		91540204
National Natural Science Foundation of China (NSFC)		31430022
National Natural Science Foundation of China (NSFC)		31471395
Ministry of Science and Technology of the People's Republic of China (MOST)		2016YFC0900300

Accessions in other database

Accession	Database name
GSE100528	NCBI

Submitter

Qingqing Shi (slqingqing@126.com)

Organization

Institute of Genetics and Developmental Biology, Chinese Academy of Sciences

Submission date

2020-06-25

Project Data

Resource name	Description
BioSample (16) show	-
SAMC197632	m6A-seq of mus musculus: P14 Mettl3 knockout brain
SAMC197631	m6A-seq of mus musculus: P14 Mettl3 knockout brain
SAMC197630	m6A-seq of mus musculus: P14 wild type brain
SAMC197629	m6A-seq of mus musculus: P14 wild type brain
SAMC197628	RNA-seq of mus musculus: P14 Mettl3 knockout brain
SAMC197627	RNA-seq of mus musculus: P14 Mettl3 knockout brain
SAMC197626	RNA-seq of mus musculus: P14 wild type brain
SAMC197625	RNA-seq of mus musculus: P14 wild type brain
SAMC197624	m6A-seq of mus musculus: P7 Mettl3 knockout brain
SAMC197623	m6A-seq of mus musculus: P7 Mettl3 knockout brain
SAMC197622	m6A-seq of mus musculus: P7 wild type brain
SAMC197621	m6A-seq of mus musculus: P7 wild type brain
SAMC197620	RNA-seq of mus musculus: P7 Mettl3 knockout brain
SAMC197619	RNA-seq of mus musculus: P7 Mettl3 knockout brain
SAMC197618	RNA-seq of mus musculus: P7 wild type brain
SAMC197617	RNA-seq of mus musculus: P7 wild type brain
GSA (1)	-
CRA002911	METTL3-mediated m6A modification is required for cerebellar development m6A modification and cerebellar development