SF3B1 mutation generates novel peptides from long non-coding RNAs
- 1City of Hope National Medical Center
Abstract
While mRNA alternative splicing caused by somatic mutation in SF3B1 is well-characterized, long non-coding RNAs (lncRNAs) impacted by this mutation are completely unknown. Here, we report long-read sequencing of full-length transcripts from cell lines with and without SF3B1 mutation. We present ALLR (Annotation of human lncRNAs using Long-Read sequencing), a computational workflow to identify and quantify lncRNAs, and to annotate their potential roles in impacting cellular functions. Harnessing matched short-read RNA sequencing and proteomic data, we demonstrate that SF3B1 mutation generates thousands of novel lncRNAs with diverse levels of alternative splicing. Moreover, SF3B1 mutation-associated lncRNAs produce translatable peptides with putative functions, immunogenicity, and potential to bind proteins with impact on cellular signalling networks. 47 lncRNAs could also be detected in primary chronic lymphocytic leukemia (CLL) samples and are associated with significant risks towards adverse disease prognosis, in conjunction with other known CLL risk factors. Our work demonstrates the utility of long-read sequencing for lncRNA research and provides a new territory of functional RNA molecules that SF3B1 mutation may use to impact cancer.
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BibTeX
@misc{bhattacharya2026sf3b1,
title = {{SF3B1 mutation generates novel peptides from long non-coding RNAs}},
author = {S. Bhattacharya and M. Fernandez and Y. Wu and M. Jin and P. Pirrotte and K. Garcia-Mansfield and T. H. Kang and Y. Zhao and N. Lammana and L. Wang},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.15.759235},
url = {https://www.biorxiv.org/content/10.64898/2026.10.15.759235v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - SF3B1 mutation generates novel peptides from long non-coding RNAs
AU - S. Bhattacharya
AU - M. Fernandez
AU - Y. Wu
AU - M. Jin
AU - P. Pirrotte
AU - K. Garcia-Mansfield
AU - T. H. Kang
AU - Y. Zhao
AU - N. Lammana
AU - L. Wang
PY - 2026
DA - 2026/10/15
PB - bioRxiv
DO - 10.64898/2026.10.15.759235
UR - https://www.biorxiv.org/content/10.64898/2026.10.15.759235v1
AB - While mRNA alternative splicing caused by somatic mutation in SF3B1 is well-characterized, long non-coding RNAs (lncRNAs) impacted by this mutation are completely unknown. Here, we report long-read sequencing of full-length transcripts from cell lines with and without SF3B1 mutation. We present ALLR (Annotation of human lncRNAs using Long-Read sequencing), a computational workflow to identify and quantify lncRNAs, and to annotate their potential roles in impacting cellular functions. Harnessing matched short-read RNA sequencing and proteomic data, we demonstrate that SF3B1 mutation generates thousands of novel lncRNAs with diverse levels of alternative splicing. Moreover, SF3B1 mutation-associated lncRNAs produce translatable peptides with putative functions, immunogenicity, and potential to bind proteins with impact on cellular signalling networks. 47 lncRNAs could also be detected in primary chronic lymphocytic leukemia (CLL) samples and are associated with significant risks towards adverse disease prognosis, in conjunction with other known CLL risk factors. Our work demonstrates the utility of long-read sequencing for lncRNA research and provides a new territory of functional RNA molecules that SF3B1 mutation may use to impact cancer.
ER -