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Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP.

ABSTRACT: The mammalian Staufen proteins (Stau1 and Stau2) mediate degradation of mRNA containing complex secondary structures in their 3'-untranslated region (UTR) through a pathway known as Staufen-mediated mRNA decay (SMD). This pathway also involves the RNA helicase UPF1, which is best known for its role in the nonsense-mediated mRNA decay (NMD) pathway. Here we present a biochemical reconstitution of the recruitment and activation of UPF1 in context of the SMD pathway. We demonstrate the involvement of UPF2, a core NMD factor and a known activator of UPF1, in SMD. UPF2 acts as an adaptor between Stau1 and UPF1, stimulates the catalytic activity of UPF1 and plays a central role in the formation of an SMD-competent mRNP. Our study elucidates the molecular mechanisms of SMD and points towards extensive cross-talk between UPF1-mediated mRNA decay pathways in cells.

SUBMITTER: Gowravaram M

PROVIDER: S-EPMC6838198 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP.

Gowravaram Manjeera M Schwarz Juliane J Khilji Sana K SK Urlaub Henning H Chakrabarti Sutapa S

Nature communications 20191107 1

The mammalian Staufen proteins (Stau1 and Stau2) mediate degradation of mRNA containing complex secondary structures in their 3'-untranslated region (UTR) through a pathway known as Staufen-mediated mRNA decay (SMD). This pathway also involves the RNA helicase UPF1, which is best known for its role in the nonsense-mediated mRNA decay (NMD) pathway. Here we present a biochemical reconstitution of the recruitment and activation of UPF1 in context of the SMD pathway. We demonstrate the involvement ...[more]

PMID: 31699982

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