Low complexity (A/C)GG repeats and m¹A methylation sites in 5' UTRs regulate gene expression

Area of Science:

• Molecular Biology
• Genomics
• Bioinformatics

Background:

• Repetitive, low-complexity (LC) motifs in biological sequences impact molecular abundance and evolution.
• The precise role of LC motifs in post-transcriptional regulation and their definitions remain unclear.

Purpose of the Study:

• To define low-complexity (LC) motifs in RNA and protein sequences.
• To investigate the association between LC motifs and transcript/protein abundance.
• To identify novel abundance-associated motifs and regulatory mechanisms.

Main Methods:

• Integrated data from GTEx, PaxDb, and IGSR projects.
• Established definitions for LC motifs in RNA and protein sequences.
• Developed a de novo method to identify abundance-associated motifs.

Main Results:

• LC motifs in the 5' untranslated region (UTR) positively correlate with transcript abundance.
• Trinucleotide repeats of (A/C)GG were identified as strongly abundance-associated motifs.
• m1A methylation sites show a strong association with both LC motifs and abundance, enhanced by unspecialized RNA-seq signatures.

Conclusions:

• Low-complexity (LC) motifs significantly regulate gene expression at the post-transcriptional level.
• Defined LC motifs and identified specific sequence patterns linked to molecular abundance.
• Revealed a link between m1A methylation, LC motifs, and gene expression regulation.