TY - JOUR

T1 - Taxonomy of introns and the evolution of minor introns

AU - Olthof, Anouk m

AU - Schwoerer, Charles F

AU - Girardini, Kaitlin N.

AU - Weber, Audrey L

AU - Doggett, Karen

AU - Mieruszynski, Stephen

AU - Heath, Joan K.

AU - Moore, Timothy E.

AU - Biran, Jakob

AU - Kanadia, Rahul N

PY - 2024

Y1 - 2024

N2 - Classification of introns, which is crucial to understanding their evolution and splicing, has historically been binary and has resulted in the naming of major and minor introns that are spliced by their namesake spliceosome. However, a broad range of intron consensus sequences exist, leading us to here reclassify introns as minor, minor-like, hybrid, major-like, major and non-canonical introns in 263 species across six eukaryotic supergroups. Through intron orthology analysis, we discovered that minor-like introns are a transitory node for intron conversion across evolution. Despite close resemblance of their consensus sequences to minor introns, these introns possess an AG dinucleotide at the –1 and –2 position of the 5′ splice site, a salient feature of major introns. Through combined analysis of CoLa-seq, CLIP-seq for major and minor spliceosome components, and RNAseq from samples in which the minor spliceosome is inhibited we found that minor-like introns are also an intermediate class from a splicing mechanism perspective. Importantly, this analysis has provided insight into the sequence elements that have evolved to make minor-like introns amenable to recognition by both minor and major spliceosome components. We hope that this revised intron classification provides a new framework to study intron evolution and splicing.

AB - Classification of introns, which is crucial to understanding their evolution and splicing, has historically been binary and has resulted in the naming of major and minor introns that are spliced by their namesake spliceosome. However, a broad range of intron consensus sequences exist, leading us to here reclassify introns as minor, minor-like, hybrid, major-like, major and non-canonical introns in 263 species across six eukaryotic supergroups. Through intron orthology analysis, we discovered that minor-like introns are a transitory node for intron conversion across evolution. Despite close resemblance of their consensus sequences to minor introns, these introns possess an AG dinucleotide at the –1 and –2 position of the 5′ splice site, a salient feature of major introns. Through combined analysis of CoLa-seq, CLIP-seq for major and minor spliceosome components, and RNAseq from samples in which the minor spliceosome is inhibited we found that minor-like introns are also an intermediate class from a splicing mechanism perspective. Importantly, this analysis has provided insight into the sequence elements that have evolved to make minor-like introns amenable to recognition by both minor and major spliceosome components. We hope that this revised intron classification provides a new framework to study intron evolution and splicing.

U2 - 10.1093/nar/gkae550

DO - 10.1093/nar/gkae550

M3 - Journal article

C2 - 38943346

VL - 52

SP - 9247

EP - 9266

JO - Nucleic acids symposium series

JF - Nucleic acids symposium series

SN - 0261-3166

IS - 15

ER -