Cancer mutations rewire the RNA methylation specificity of METTL3-METTL14.

Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most -methyladenosine (mA) modifications in messenger RNAs (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context for mA can promote oncogenesis.

Effects of METTL3-METTL14 on primary microRNA processing by Drosha-DGCR8.

MicroRNAs modulate most protein-coding genes, and many are regulated during maturation. Chemical modifications of primary transcripts containing microRNAs have been implicated in altering Microprocessor processing efficiency, a key initiating endonucleolytic step performed by Drosha and DGCR8. METTL3-METTL14 produces N -methyladenosine which is the most common methylation for mRNAs.

Completion of LINE integration involves an open '4-way' branched DNA intermediate.

Long Interspersed Elements (LINEs), also known as non-LTR retrotransposons, encode a multifunctional protein that reverse transcribes its mRNA into DNA at the site of insertion by target primed reverse transcription. The second half of the integration reaction remains very poorly understood. Second-strand DNA cleavage and second-strand DNA synthesis were investigated in vitro using purified components from a site-specific restriction-like endonuclease (RLE) bearing LINE.