Pluto Bioinformatics

GSE102204: Transcriptome and translatome profiling from brains of a mouse model of severe SMA

Bulk RNA sequencing

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, with an incidence of around 1 in 6,000-10,000 live births. SMA is caused by low levels of full-length survival of motor neuron protein (SMN). Approximately 95% of SMA cases in humans are caused by homozygous deletion of SMN1, with a smaller number caused by discrete mutations within the gene. In concert with other RNA binding proteins, SMN forms complexes both in the nucleus and the cytoplasm of neurons. As such, SMN protein has housekeeping roles in the assembly of ribonucleoprotein (RNP) complexes. In addition, SMN localises to dendrites, synapses and axons in vivo and in vitro, where it is part of messenger RNP (mRNP) complexes with well-known roles in the transport of mRNA. These cellular processes are tightly linked to local translation, suggesting that SMN may play a pivotal role in its regulation. We employed next generation sequencing (NGS) to identify and quantify RNAs associated with polysomes (POL-Seq) in parallel with total cytoplasmic RNA (RNA-Seq) in an established mouse model of severe SMA at both early and late-symptomatic stages. This approach enables the simultaneous identification of variations in RNA populations at both translatome (RNAs engagement with polysomes) and transcriptome (steady state cytoplasmic RNAs) levels.; Keywords: motor neuron disease, spinal muscular atrophy, SMA,SMN, translation, polysome profiling, POL-Seq, RNA-Seq SOURCE: Toma Tebaldi (t.tebaldi@unitn.it) - University of Trento