FBXW7β isoform drives transcriptional activation of the proinflammatory TNF cluster in human pro-B cells.

ABSTRACT: Noncanonical exon usage plays many important roles in cellular phenotypes, but its contribution to human B-cell development remains sketchily understood. To fill this gap, we collected various B-cell fractions from bone marrow (BM) and tonsil donors, performed RNA sequencing, and examined transcript variants. We identified 150 genes that harbor local splicing variations in all pairwise comparisons. One of them encodes FBXW7, an E3 ubiquitin ligase implicated as a driver in several blood cancers. Surprisingly, we discovered that in normal human pro-B cells, the predominant transcript used an alternative first exon to produce the poorly characterized FBXW7β isoform, previously thought to be restricted to neural tissues. The FBXW7β transcript was also abundant in cell lines and primary sample

SUBMITTER: Yang SY 

PROVIDER: S-EPMC10111352 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature