A common class of transcripts with 5'-intron depletion, distinct early coding sequence features, and...

Area of Science:

• Molecular Biology
• Genomics
• RNA Biology

Background:

• Introns within 5' untranslated regions (5'UTRs) are present in 35% of human transcripts.
• The distribution of 5'UTR introns is non-random, with fewer found in transcripts encoding secreted, membrane-bound, or mitochondrial proteins.
• Transcripts lacking 5'UTR introns often contain specific RNA sequence elements in their early coding regions.

Purpose of the Study:

• To develop a model for understanding the relationship between coding region sequence and 5'UTR intron status.
• To identify and characterize a distinct class of transcripts defined by the absence of 5'UTR introns and specific coding region features.

Main Methods:

• Development of a classifier using early coding region sequence features to predict 5'UTR intron status with >80% accuracy.
• Analysis of sequence features, translation efficiency, RNA modifications, and protein binding in the identified transcript class.

Main Results:

• Identification of a widespread class of transcripts, termed '5IM' (5' proximal-intron-minus-like-coding regions), comprising 21% of human RefSeq transcripts.
• 5IM transcripts are characterized by non-AUG start codons, increased secondary structure near the 5' cap, greater reliance on eIF4E for translation, and association with ER-proximal ribosomes.
• Enrichment of N1-methyladenosines and noncanonical binding by the exon junction complex (EJC) at 5' proximal positions in 5IM transcripts.

Conclusions:

• A distinct class of approximately 20% of human transcripts (5IM) is defined by the depletion of 5' proximal introns and specific early coding region sequence features.
• These features are associated with reduced translation efficiency, unique RNA modifications (N1-methyladenosines), and distinct RNA-protein interactions (EJC binding).
• The findings suggest a novel regulatory mechanism influencing gene expression through coding region sequences and RNA modifications in a significant portion of the human transcriptome.