TY - CHAP

T1 - Functions and Dynamics of Methylation in Eukaryotic mRNA

AU - Chen, Mingjia

AU - Witte, Claus-Peter

N1 - Funding Information: Acknowledgement We apologize to those colleagues whose work could not be cited due to space limitations. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research foundation) grant 416961553 (CH 2292/1-1) to M.C. and the Leibniz University Hannover (Wege in die Forschung II to M.C.).

PY - 2019

Y1 - 2019

N2 - Eukaryotic messenger RNA (mRNA) contains non-canonical nucleosides, which are modified mostly by methylation. Although some modifications are known for decades, advances in high-throughput sequencing and mass spectrometric techniques now have allowed to elucidate transcriptome wide methylation patterns. The discovery of methyltransferases that write and demethylases that erase methylations in a sequence-specific manner, as well as reader proteins that recognize these modifications leading to a specific biological response, has triggered wide attention converting the research field of mRNA methylation into a current hotspot in molecular biology. Most research has focussed on N 6-methyladenosine (m 6A), which is the most abundant modification in eukaryotic mRNA. Therefore, this overview has a focus on m 6A summarizing the current knowledge on how specific m 6A patterns are generated and how they are recognized and translated into biological outputs like alternative splicing, altered transcript stability, or modified translational activity of mRNAs. The distribution patterns of other methylations in mRNA, such as N 1-methyladenosine (m 1A), 5-methylcytidine (m 5C) and 5-hydroxymethylcytidine (hm 5C) have also been mapped in recent years. We review the current knowledge regarding these and other minor eukaryotic mRNA methylations and provide an outlook suggesting potential future research directions.

AB - Eukaryotic messenger RNA (mRNA) contains non-canonical nucleosides, which are modified mostly by methylation. Although some modifications are known for decades, advances in high-throughput sequencing and mass spectrometric techniques now have allowed to elucidate transcriptome wide methylation patterns. The discovery of methyltransferases that write and demethylases that erase methylations in a sequence-specific manner, as well as reader proteins that recognize these modifications leading to a specific biological response, has triggered wide attention converting the research field of mRNA methylation into a current hotspot in molecular biology. Most research has focussed on N 6-methyladenosine (m 6A), which is the most abundant modification in eukaryotic mRNA. Therefore, this overview has a focus on m 6A summarizing the current knowledge on how specific m 6A patterns are generated and how they are recognized and translated into biological outputs like alternative splicing, altered transcript stability, or modified translational activity of mRNAs. The distribution patterns of other methylations in mRNA, such as N 1-methyladenosine (m 1A), 5-methylcytidine (m 5C) and 5-hydroxymethylcytidine (hm 5C) have also been mapped in recent years. We review the current knowledge regarding these and other minor eukaryotic mRNA methylations and provide an outlook suggesting potential future research directions.

KW - 2′-O-methylation (N )

KW - 3-methylcytidine (m C)

KW - 7-methylguannosine (m G)

KW - Demethylase

KW - Methyltransferase

KW - N -acetylcytidine (ac C)

KW - N -mAMP

KW - N -methyl AMP deaminase (MAPDA)

KW - YTH family proteins

UR - http://www.scopus.com/inward/record.url?scp=85083652154&partnerID=8YFLogxK

U2 - 10.1007/978-3-030-14792-1_13

DO - 10.1007/978-3-030-14792-1_13

M3 - Contribution to book/anthology

SN - 978-3-030-14794-5

SN - 978-3-030-14791-4

T3 - RNA Technologies

SP - 333

EP - 351

BT - The DNA, RNA, and Histone Methylomes

CY - Cham

ER -