Novel read‐through fusion transcript Bcl2l2‐Pabpn1 in glioblastoma cells

Abstract

Read‐through fusion transcripts have recently been identified as chimeric RNAs and have since been linked to tumour growth in some cases. Many fusion genes generated by chromosomal rearrangements have been described in glioblastoma. However, read‐through fusion transcripts between neighbouring genes in glioblastoma remain unexplored. We performed paired‐end RNA‐seq of rat C6 glioma cells and normal cells and discovered a read‐through fusion transcript Bcl2l2‐Pabpn1 in which exon 3 of Bcl‐2‐like protein 2 (Bcl2l2) fused to exon 2 of Polyadenylate‐binding protein 1 (Pabpn1). This fusion transcript was found in both human glioblastoma and normal cells. Unlike other fusions reported in glioblastoma, Bcl2l2‐Pabpn1 appeared to result from RNA processing rather than genomic rearrangement. Bcl2l2‐Pabpn1 fusion transcript encoded a fusion protein with BH4, BCL and RRM domains. Functionally, Bcl2l2‐Pabpn1 knockdown by targeting its fusion junction decreased its expression, and suppressed cell proliferation, migration and invasion in vitro. Mechanistically, Bcl2l2‐Pabpn1 blocked Bax activity and activated PI3K/AKT pathway to promote glioblastoma progression. Together, our work characterized a glioblastoma‐associated Bcl2l2‐Pabpn1 fusion transcript shared by humans and rats.

Novel MFSD7‐ATP5I fusion promotes migration and invasion of human sarcoma

“…21 However, fusion transcripts without corresponding genomic changes have been reported in many cancer types. 11,14,[22][23][24] Choi et al 24 reported that PHOSPHO2-KLHL23 read-through transcript increases KLHL23…”

“…In addition, read‐through fusion transcripts are abundantly found in normal tissue 21 . However, fusion transcripts without corresponding genomic changes have been reported in many cancer types 11,14,22–24 . Choi et al 24 reported that PHOSPHO2‐KLHL23 read‐through transcript increases KLHL23 protein expression and increases cell proliferation and resistance to anticancer drug treatment.…”

“…Choi et al 24 reported that PHOSPHO2‐KLHL23 read‐through transcript increases KLHL23 protein expression and increases cell proliferation and resistance to anticancer drug treatment. Zhang et al 23 reported that the Bcl2l2‐Pabpn1 read‐through fusion transcript, although found in normal cells, encodes a fusion protein that promotes the progression of glioblastoma. Therefore, discovering and charicterizing a new fusion transcript can enhance our understanding of cancer biology.…”

Uncovering the Localization and Function of a Novel Read-Through Transcript ‘TOMM40-APOE’

“…Various read-through transcripts have been identified with the recent progress in genome analysis, and it has been suggested that these chimeric transcripts can be translated to generate fusion proteins that exhibit new subcellular localization or have special properties [ 17 , 18 ]. In fact, in this study, the fusion of the mitochondrial protein TOMM40 with the secreted protein APOE was found to generate a new mitochondrial protein without the properties of the latter.…”

Versatile RNA: overlooked gems of the transcriptome

“…CHFR-GOLGA3 and BCL2L2-PABPN1 transcripts are highly expressed in bladder tumours relative to adjacent normal tissue [50]. The BCL2L2-PABPN1 transcript, with oncogenic activity, is also detected in glioblastomas [51]. The functionality of read-through transcripts, whether their mode of action is through the transcript or a protein product, remains to be investigated.…”