MeT-DB: a database of transcriptome methylation in mammalian cells
Hui Liu
2
Mario A Flores
1
Jia Meng
0
Lin Zhang
2
Xinyu Zhao
5
Manjeet K. Rao
4
5
Yidong Chen
3
5
Yufei Huang
1
3
0
Department of Biological Sciences, Xi'an Jiaotong-Liverpool University
,
Suzhou, Jiangsu 215123
,
China
1
Department of Electrical and Computer Engineering, University of Texas at San Antonio
,
TX 78249-0669
,
USA
2
School of Information and Electrical Engineering, China University of Mining and Technology
,
Xuzhou, Jiangsu 221116
,
China
3
Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio
,
TX 78229
,
USA
4
Department of Cellular Structural Biology, University of Texas Health Science Center at San Antonio
,
TX 78229
,
USA
5
Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio
,
TX 78229
,
USA
Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. The MethylTranscriptome DataBase (MeT-DB, http://compgenomics.utsa.edu/ methylation/) is the first comprehensive resource for N6-methyladenosine (m6A) in mammalian transcriptome. It includes a database that records publicaly available data sets from methylated RNA immunoprecipitation sequencing (MeRIP-Seq), a recently developed technology for interrogating m6A methyltranscriptome. MeT-DB includes 300k m6A methylation sites in 74 MeRIP-Seq samples from 22 different experimental conditions predicted by exomePeak and MACS2 algorithms. To explore this rich information, MeT-DB also provides a genome browser to query and visualize context-specific m6A methylation under different conditions. MeT-DB also includes the binding site data of microRNA, splicing factor and RNA binding proteins in the browser window for comparison with m6A sites and for exploring the potential functions of m6A. Analysis of differential m6A methylation and the related differential gene expression under two conditions is also available in the browser. A global perspective of the genome-wide distribution of m6A methylation in all the data is provided in circular ideograms, which also act as a navigation portal. The query results and the entire data set can be exported to assist publication and additional analysis.
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The past decades have witnessed the great progress in DNA
methylation research (1,2). Yet, research on methylation in
transcripts is still at its very early stage. Thus far,
N6-methyladenosine (m6A) is known to be the most abound form of
methylation in transcripts. The recent surge of interest in
transcriptome-wide m6A methylation stemmed largely from
two seminal studies (3,4), where a new enrichment-based
high-throughput method called MeRIP-Seq, or methylated
RNA immunoprecipitation sequencing, was introduced to
identify for the first time the presence of over 12 000 m6A
sites in about 20% of mammalian genes.
Transcriptomewide analysis also revealed that m6A sites reside in the
highly evolutionarily conserved regions with a consensus
sequence motif of RRACH that is also conserved between
human and mouse, suggesting the possibility of conserved
regulatory functions of m6A. A series of subsequent papers
that used MeRIP-Seq and other high-throughput methods
have started to produce evidences and new hypotheses on
involvement of m6A in regulating many functions (5).
Currently, analysis of m6A distribution in mRNA
showed that m6A is enriched in the 3 untranslated
region (UTR) and near stop codon. Among 3 UTRs that
contain an m6A site, two-thirds also have at least one
TargetScan-predicted miRNA binding site, suggesting that
m6A might be involved in miRNA-mediated gene
silencing. Existing studies also suggested that m6A recruits
different RNA binding proteins (RBP) to mediate its own
methylation cycle and to regulate various other cellular
functions. For instance, transcriptome m6A methylation is
known to be catalyzed by the methyltransferase complex
that includes methyltransferase-like 3 (METTL3), Wilms
tumor 1-associated protein (WTAP) and METTL14 (6).
In*To whom correspondence should be addressed. Tel: +210 4586270; Fax: +210 4585947; Email:
Correspondence may also be addressed to Yidong Chen. Tel: +210 5629163; Fax: +210 5629014; Email:
The authors wish it to be known that, in their opinion, the first three authors should be regarded as Joint First Authors.
terestingly, WTAP is a pre-mRNA-splicing regulator and
a recent PAR-CLIP analysis also showed that METTL3
binding sites reside mostly in intronic regions of pre-mRNA
(7). These evidences suggest a likely involvement of m6A
in splicing but the splicing factors and the mechanism by
which it regulates splicing is unclear. In addition to
splicing, m6A has also been shown to promote mRNA
degradation through recruiting the human YTH domain
family 2 protein to the methylated mRNA and this
recruitment redirects mRNA to mRNA decay compartment as
opposed to ribosome for translation (8). In contrast, m6A
was also suggested to stabilize mRNA, where loss of m6A
in an (...truncated)