A SteMNess perspective of survival motor neuron function: splicing factors in stem cell biology and disease

Abstract

Genome-wide analyses of metazoan messenger RNA (mRNA) species are unveiling the extensive transcriptional diversity generated by alternative splicing (AS). Research is also beginning to identify the splicing factors and AS events required to maintain the balance between stem cell renewal (i.e stemness properties) and differentiation. One set of proteins at the center of spliceosome biogenesis are the survival motor neuron (SMN) complex constituents, which have a critical role in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs) in all cells. In this review we discuss what is currently known about how AS controls pluripotency and cell fate and consider how an increased requirement for splicing factors, including SMN, helps to maintain an enrichment of stem cell-specific AS events. Furthermore, we highlight studies showing that mutations in specific splicing factors can lead to the aberrant development, and cause targeted degeneration of the nervous system. Using SMN as an example, we discuss the perspective of how stem cell-specific changes in splicing factors can lead to developmental defects and the selective degeneration of particular tissues. Finally we consider the expanding role of SMN, and other splicing factors, in the regulation of gene expression in stem cell biology, thereby providing insight into a number of debilitating diseases.

Keywords

stem cells / splicing / survival motor neuron (SMN) / spinal muscular atrophy (SMA)

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Compliance with ethics guidelines

Stuart J Grice and Ji-long Liu declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg