RNA-processing Proteins May Be Factors in Development of SMA, Pilot Study Suggests

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by Alice Melão |

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RNA-processing proteins, including the FUS protein, may be involved in the underlying molecular mechanism that causes spinal muscular atrophy (SMA), a pilot study suggests.

The study, “The expression of SMN1, MART3, GLE1 and FUS genes in spinal muscular atrophy,” was published in the journal Folia Histochemica et Cytobiologica.

Several complex steps exist before a protein can be produced. DNA is first transformed into RNA, and eventually, through a process called translation, into a protein. All information contained within genes (DNA) is ultimately translated into proteins.

SMA is a progressive neurodegenerative disorder caused by the disruption of the SMN1 gene, which provides instructions for making the SMN protein. This protein is involved in the processing of RNA molecules, including their maturation, transport, and translation into functional proteins.

Several other genes, including C9ORF72, TARDBP, and CHMP2Bs, implicated in the regulation of RNA processing, have been linked to neurodegenerative disorders. These genes have also been associated with the development of both frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

The study assessed the potential relationship between the expression of the SMN1 gene with three other genes involved in RNA processing and protein production — GLE1, MATR3, and FUS — and that have been previously identified as risk factors for neurodegenerative disorders. Gene expression is the process by which information in a gene is synthesized to create a working product, like a protein.

The research team analyzed the expression of these genes in skin cells, collected from three patients diagnosed with SMA type 1 (all 3-year-old boys), and from three age-matched healthy volunteers.

As expected, SMA patients had very low, or even absent, SMN1 expression. MATR3 and GLE1 levels were both found to be about half of that reported in healthy controls. In contrast, FUS gene levels were about threefold higher in SMA patients than in the control group.

Further analysis revealed that FUS gene levels were highly correlated with SMN1 levels in SMA patients, suggesting a potential role of the FUS protein in the progression of SMA. Weaker associations between MATR3 and GLE1 genes with SMN1 were also detected.

The researchers believe these findings further “emphasize the importance” of changes in RNA-processing proteins as having a key role in SMA’s underlying mechanism. “It is possible that these genes can be developed as biomarkers for SMA disease diagnosis and eventually, as targets of drug treatments against SMA,” they said.

Additional studies are still warranted to explore if the proteins for which these genes provide instructions could be used as monitoring biomarkers in the early stages of pregnancy “to diagnose SMA, and thus increase the survival rate, if the treatment is available,” they concluded.