TY - JOUR
T1 - Circular stable intronic RNAs possess distinct biological features and are deregulated in bladder cancer
AU - Rasmussen, Asta M.
AU - Okholm, Trine Line H.
AU - Knudsen, Michael
AU - Vang, Søren
AU - Dyrskjøt, Lars
AU - Hansen, Thomas B.
AU - Pedersen, Jakob S.
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of NAR Cancer.
PY - 2023/9
Y1 - 2023/9
N2 - Until recently, intronic lariats were regarded as short-lasting splicing byproducts with no apparent function; however, increasing evidence of stable derivatives suggests regulatory roles. Yet little is known about their characteristics, functions, distribution, and expression in healthy and tumor tissue. Here, we profiled and characterized circular stable intronic sequence RNAs (sisRNAs) using total RNA-Seq data from bladder cancer (BC; n = 457, UROMOL cohort), healthy tissue (n = 46), and fractionated cell lines (n = 5). We found that the recently-discovered full-length intronic circles and the stable lariats formed distinct subclasses, with a surprisingly high intronic circle fraction in BC (∼45%) compared to healthy tissues (0-20%). The stable lariats and their host introns were characterized by small transcript sizes, highly conserved BP regions, enriched BP motifs, and localization in multiple cell fractions. Additionally, circular sisRNAs showed tissue-specific expression patterns. We found nine circular sisRNAs as differentially expressed across early-stage BC patients with different prognoses, and sisHNRNPK expression correlated with progression-free survival. In conclusion, we identify distinguishing biological features of circular sisRNAs and point to specific candidates (incl. sisHNRNPK, sisWDR13 and sisMBNL1) that were highly expressed, had evolutionary conserved sequences, or had clinical correlations, which may facilitate future studies and further insights into their functional roles.
AB - Until recently, intronic lariats were regarded as short-lasting splicing byproducts with no apparent function; however, increasing evidence of stable derivatives suggests regulatory roles. Yet little is known about their characteristics, functions, distribution, and expression in healthy and tumor tissue. Here, we profiled and characterized circular stable intronic sequence RNAs (sisRNAs) using total RNA-Seq data from bladder cancer (BC; n = 457, UROMOL cohort), healthy tissue (n = 46), and fractionated cell lines (n = 5). We found that the recently-discovered full-length intronic circles and the stable lariats formed distinct subclasses, with a surprisingly high intronic circle fraction in BC (∼45%) compared to healthy tissues (0-20%). The stable lariats and their host introns were characterized by small transcript sizes, highly conserved BP regions, enriched BP motifs, and localization in multiple cell fractions. Additionally, circular sisRNAs showed tissue-specific expression patterns. We found nine circular sisRNAs as differentially expressed across early-stage BC patients with different prognoses, and sisHNRNPK expression correlated with progression-free survival. In conclusion, we identify distinguishing biological features of circular sisRNAs and point to specific candidates (incl. sisHNRNPK, sisWDR13 and sisMBNL1) that were highly expressed, had evolutionary conserved sequences, or had clinical correlations, which may facilitate future studies and further insights into their functional roles.
UR - http://www.scopus.com/inward/record.url?scp=85168566093&partnerID=8YFLogxK
U2 - 10.1093/narcan/zcad041
DO - 10.1093/narcan/zcad041
M3 - Journal article
C2 - 37554968
AN - SCOPUS:85168566093
SN - 2632-8674
VL - 5
JO - NAR cancer
JF - NAR cancer
IS - 3
M1 - zcad041
ER -