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Abstract
N
6
-methyladenosine (m
6
A) is the most prevalent modification in eukaryotic RNAs. The biological importance of m
6
A relies on m
6
A readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of m
6
A readers are involved in the m
6
A recognition on RNAs. Here we discover that the long noncoding RNA (lncRNA)
LINC00266-1
encodes a 71-amino acid peptide. The peptide mainly interacts with the RNA-binding proteins, including the m
6
A reader IGF2BP1, and is thus named “RNA-binding regulatory peptide” (RBRP). RBRP binds to IGF2BP1 and strengthens m
6
A recognition by IGF2BP1 on RNAs, such as
c-Myc
mRNA, to increase the mRNA stability and expression of
c-Myc
, thereby promoting tumorigenesis. Cancer patients with RBRP
high
have a poor prognosis. Thus, the oncopeptide RBRP encoded by
LINC00266-1
is a regulatory subunit of m
6
A readers and strengthens m
6
A recognition on the target RNAs by the m
6
A reader to exert its oncogenic functions.