Comprehensive analysis of the Kinetoplastea intron landscape reveals a novel intron-containing gene and the first exclusively trans-splicing eukaryote

TY - JOUR

T1 - Comprehensive analysis of the Kinetoplastea intron landscape reveals a novel intron-containing gene and the first exclusively trans-splicing eukaryote

AU - Kostygov, Alexei Yu

AU - Skýpalová, Karolína

AU - Kraeva, Natalia

AU - Kalita, Elora

AU - McLeod, Cameron

AU - Yurchenko, Vyacheslav

AU - Field, Mark C.

AU - Lukeš, Julius

AU - Butenko, Anzhelika

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024/12/3

Y1 - 2024/12/3

N2 - Background: In trypanosomatids, a group of unicellular eukaryotes that includes numerous important human parasites, cis-splicing has been previously reported for only two genes: a poly(A) polymerase and an RNA helicase. Conversely, trans-splicing, which involves the attachment of a spliced leader sequence, is observed for nearly every protein-coding transcript. So far, our understanding of splicing in this protistan group has stemmed from the analysis of only a few medically relevant species. In this study, we used an extensive dataset encompassing all described trypanosomatid genera to investigate the distribution of intron-containing genes and the evolution of splice sites. Results: We identified a new conserved intron-containing gene encoding an RNA-binding protein that is universally present in Kinetoplastea. We show that Perkinsela sp., a kinetoplastid endosymbiont of Amoebozoa, represents the first eukaryote completely devoid of cis-splicing, yet still preserving trans-splicing. We also provided evidence for reverse transcriptase-mediated intron loss in Kinetoplastea, extensive conservation of 5′ splice sites, and the presence of non-coding RNAs within a subset of retained trypanosomatid introns. Conclusions: All three intron-containing genes identified in Kinetoplastea encode RNA-interacting proteins, with a potential to fine-tune the expression of multiple genes, thus challenging the perception of cis-splicing in these protists as a mere evolutionary relic. We suggest that there is a selective pressure to retain cis-splicing in trypanosomatids and that this is likely associated with overall control of mRNA processing. Our study provides new insights into the evolution of introns and, consequently, the regulation of gene expression in eukaryotes.

AB - Background: In trypanosomatids, a group of unicellular eukaryotes that includes numerous important human parasites, cis-splicing has been previously reported for only two genes: a poly(A) polymerase and an RNA helicase. Conversely, trans-splicing, which involves the attachment of a spliced leader sequence, is observed for nearly every protein-coding transcript. So far, our understanding of splicing in this protistan group has stemmed from the analysis of only a few medically relevant species. In this study, we used an extensive dataset encompassing all described trypanosomatid genera to investigate the distribution of intron-containing genes and the evolution of splice sites. Results: We identified a new conserved intron-containing gene encoding an RNA-binding protein that is universally present in Kinetoplastea. We show that Perkinsela sp., a kinetoplastid endosymbiont of Amoebozoa, represents the first eukaryote completely devoid of cis-splicing, yet still preserving trans-splicing. We also provided evidence for reverse transcriptase-mediated intron loss in Kinetoplastea, extensive conservation of 5′ splice sites, and the presence of non-coding RNAs within a subset of retained trypanosomatid introns. Conclusions: All three intron-containing genes identified in Kinetoplastea encode RNA-interacting proteins, with a potential to fine-tune the expression of multiple genes, thus challenging the perception of cis-splicing in these protists as a mere evolutionary relic. We suggest that there is a selective pressure to retain cis-splicing in trypanosomatids and that this is likely associated with overall control of mRNA processing. Our study provides new insights into the evolution of introns and, consequently, the regulation of gene expression in eukaryotes.

KW - Introns

KW - Kinetoplastea

KW - Poly(A) polymerase

KW - RNA helicase

KW - RNA-binding protein

KW - Splicing

KW - Trypanosomatidae

UR - https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1102159

UR - https://www.scopus.com/pages/publications/85211382369

U2 - 10.1186/s12915-024-02080-z

DO - 10.1186/s12915-024-02080-z

M3 - Article

C2 - 39627879

AN - SCOPUS:85211382369

SN - 1741-7007

VL - 22

JO - BMC Biology

JF - BMC Biology

M1 - 281

ER -