RNAs play key role in protein aggregation and in neurodegenerative disease, according to new research

RNAs play key role in protein aggregation and in neurodegenerative disease, according to new research

News from CRG

CRG researcher and ICREA Research Professor Gian Gaetano Tartaglia and CRG Alumni Teresa Botta-Orfila, and currently at IDIBAPS, wanted to understand how RNA can promote aggregation. In their research, published in the journal Cell Reports, they discovered that specific RNAs do indeed interact with many proteins within cells, and that these RNAs have distinct properties – they are structured, have a long area of untranslated genetic code called a UTR region, and often contain several repeats of genetic code (called CGG expansions) within them.  

New research reveals RNAs, which are crucial for cells to produce proteins, are also involved in protein aggregation, where proteins do not fold properly and ‘clump’ together into aggregates. If cells cannot clear these away, they become toxic and prevent cells working properly. This discovery, led by scientists at the CRG in Barcelona, reveals that RNAs act as a ‘scaffold’ to hold several proteins that stick to RNAs together, and that certain RNA molecules with distinct properties attract more proteins and encourage proteins to aggregate. They also investigated how an RNA called FMR1 is implicated in a neurodegenerative disease called Fragile X Tremor Syndrome, or FXTAS.

Many neurodegenerative diseases are linked to protein aggregation, including amyotrophic lateral sclerosis and Alzheimer’s disease. We know that proteins can form toxic aggregates, but until now, the contribution of nucleic acid molecules such as RNA has been up for debate.


More information:
CRG Website

Reference article:
Cid-Samper, F., Gelabert-Baldrich, M., Lang, B., Lorenzo-Gotor, N., Delli Ponti, R., Severijnen, L-A., Bolognesi, B., Gelpi, E., Hukema, RK., Botta-Orfila, T., Gaetano Tartaglia, G (2018). An Integrative Study of Protein-RNA Condensates Identifies Scaffolding RNAs and Reveals Players in Fragile X-Associated Tremor/Ataxia Syndrome. Cell Reports 25, 3422–3434