Intron lariat spliceosomes convert lariats to true circles: implications for intron transposition

Area of Science:

• Molecular Biology
• RNA Biology
• Genomics

Background:

• Circular intron RNAs (circRNAs) are rare, full-length molecules distinct from lariats.
• The biogenesis of these circRNAs remains largely uncharacterized.
• Previous studies have reported their existence across various species.

Purpose of the Study:

• To elucidate the formation mechanism of full-length circular intron RNAs.
• To investigate the role of the spliceosome in circRNA biogenesis.
• To determine if this mechanism is conserved across eukaryotes.

Main Methods:

• Utilized Saccharomyces cerevisiae (yeast) as a model organism.
• Documented full-length and processed circular RNAs from multiple introns.
• Investigated the catalytic activity of the intron lariat spliceosome (ILS).

Main Results:

• Identified a novel catalytic activity of the ILS responsible for circRNA formation.
• Demonstrated that the 3'-OH of the lariat tail attacks the branch point, forming a 3'-5' linked circle.
• Observed analogous circRNA formation in human U2 and U12 spliceosomes, indicating conservation.

Conclusions:

• The spliceosome possesses post-splicing catalytic activity that generates circular intron RNAs.
• This newly identified mechanism provides insight into RNA processing pathways.
• The findings suggest a potential role for spliceosome activity in intron transposition and eukaryotic genome evolution.