Variant U1 snRNAs contribute to cell cycle and differentiation control of human iPS cells

The maintenance of stem cell identity, as well as the differentiation of stem cells into any lineage, requires precise regulation of gene expression. Despite intensive research, our understanding of these regulatory processes remains incomplete. Here, we focus on the understudied paralogs of the U1 small nuclear RNA gene known as variant U1 snRNAs. By generating isogenic knockout lines of human induced pluripotent stem cells for different variant U1s, we show that their loss profoundly changes both gene expression and cell cycle profiles. These effects manifest alongside alternative splicing patterns, including those involving recursive splicing sites, and lead to differential availability of stem cell regulators. Together, our results shed new light on the functional roles of variant U1 snRNAs and further our understanding of the programs controlling human pluripotency.