RNA modulates aggregation of the recombinant mammalian prion protein by direct interaction

Manuscript title: Direct involvement of RNA in mammalian prion protein aggregation: Involvement of RNA in rPrP aggregation
Recent studies have proposed that nucleic acids act as potential cofactors for protein aggregation and prionogenesis. By means of sedimentation, transmission electron microscopy, circular dichroism, static and dynamic light scattering, we have studied how RNA can influence the aggregation of the murine recombinant prion protein (rPrP). We find that RNA, independent of its sequence, source and size, modulates rPrP aggregation in a bimodal fashion, affecting both the extent and the rate of rPrP aggregation in a concentration dependent manner. Analogous to RNA-induced liquid-liquid phase transitions observed for other proteins implicated in neurodegenerative diseases, high protein to RNA ratios stimulate rPrP aggregation, while low ratios suppress it. However, the latter scenario also promotes formation of soluble oligomeric aggregates capable of seeding de novo rPrP aggregation. Furthermore, RNA co-aggregates with rPrP and thereby gains partial protection from RNase digestion. Our results also indicate that rPrP interacts with the RNAs with its N-terminus. In summary, this study elucidates the proposed adjuvant role of RNA in prion protein aggregation and propagation, and thus advocates an auxiliary role of the nucleic acids in protein aggregation in general.

Gomes, Mariana P. B.Fiocruz MS, Biomanguinhos, Inst Tecnol Imunobiol, BR-21040900 Rio De Janeiro, Brazil (författare)
Cordeiro, YraimaUniv Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, Brazil (författare)
Ferreira, Natalia C.Univ Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, Brazil;NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT USA (författare)
Felix Valadao, Leticia P.Univ Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, Brazil (författare)
Ascari, Lucas M.Univ Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, Brazil (författare)
Rangel, Luciana P.Univ Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, Brazil (författare)
Silva, Jerson L.Univ Fed Rio de Janeiro, Inst Nacl Ciencia Tecnol Biol Estrutural & Bioima, Inst Bioquim Med Leopoldo Meis, BR-21941902 Rio De Janeiro, Brazil (författare)
Sanyal, SuparnaUppsala universitet,Molekylärbiologi(Swepub:uu)sucsa102 (författare)
Uppsala universitetMolekylärbiologi (creator_code:org_t)

Av författaren/redakt...: Kovachev, Petar ...; Gomes, Mariana P ...; Cordeiro, Yraima; Ferreira, Natali ...; Felix Valadao, L ...; Ascari, Lucas M.; visa fler...; Rangel, Luciana ...; Silva, Jerson L.; Sanyal, Suparna; visa färre...

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