Potential G-quadruplex forming sequences and N6-methyladenosine colocalize at human pre-mRNA intron splice sites

Using bioinformatic analysis of published data, we identify in human mRNA that potential G-quadruplex forming sequences (PQSs) colocalize with the epitranscriptomic modifications N6-methyladenosine (m6A), pseudouridine ({Psi}), and inosine (I). A deeper analysis of the colocalized m6A and PQSs found them intronic in pre-mRNA near 5' and 3' splice sites. The loop lengths and sequence context of the m6A-bearing PQSs found short loops most commonly comprised of A nucleotides. This observation is consistent with literature reports of intronic m6A found in SAG (S = C or G) consensus motifs that are also recognized by splicing factors. The localization of m6A and PQSs in pre-mRNA at intron splice junctions suggests that these features could be involved in alternative mRNA splicing. A similar analysis for PQSs around sites of {Psi} installation or A-to-I editing in mRNA also found a colocalization; however, the frequency was less than that observed with m6A. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/939116v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@c5fdf3org.highwire.dtl.DTLVardef@a37482org.highwire.dtl.DTLVardef@136280forg.highwire.dtl.DTLVardef@8023ab_HPS_FORMAT_FIGEXP M_FIG C_FIG