Molecular Biology

Prions: A New Part to Play

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Science  04 May 2012:
Vol. 336, Issue 6081, pp. 520
DOI: 10.1126/science.336.6081.520-b
CREDIT: GIBBINGS ET AL., NAT. STRUCT. MOL. BIOL. 19, 10.1038/NSMB.2273 (2012)

MicroRNAs (miRNAs) are small noncoding RNAs that, when part of a miRNA-induced silencing complex (miRISC), repress the expression of fully or partially complementary mRNAs. Argonaute (Ago) proteins bind miRNAs and form the heart of the silencing machinery. Intriguingly, plasma membrane–associated forms of the human prion protein (PrPC), which is associated with neurodegenerative diseases in humans, also interact with components of the miRNA pathway.

Gibbings et al. show that a transmembrane form of PrPC exposes an AGO anchor sequence in the cytoplasm and that this repeat binds AGO1 and AGO2. These PrPC-AGO complexes are found on vesicles in cells that resemble multivesicular bodies (MVBs). During miRNA maturation, AGO protein bound to miRNA must be transferred from the RISC-loading complex (RLC) to the miRISC silencing complex. PrPC binds components of both the RLC and the miRISC but seems to do so in distinct cellular locations. PrPC promotes the association of AGO with the miRISC and/or the stability of this complex. Indeed, PrPC is required for effective miRNA silencing of a number of target mRNAs. PrPC may do this through subcellular trafficking, as it seems to increase the interaction between MVBs and AGO-rich structures, such as P or GW bodies, thence promoting shuttling of AGO between the RISC-loading complex and the miRNA-induced silencing complex.

Nat. Struct. Mol. Biol. 19, 10.1038/nsmb.2273 (2012).

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