Biology:Staufen-mediated mRNA decay

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Short description: Metabolic pathway leading to mRNA degradation

Staufen-mediated mRNA decay (SMD) is a metabolic pathway that leads to degradation of specific mRNA transcripts. According to bioinformatic predictations, more than 1,000 mRNA transcripts could potentially be target by SMD.[1] SMD occurs when Staufen protein binds to stem-loop elements in the 3'UTR.

Staufen-mediated mRNA decay

This staufen/RNA complex is targeted by several proteins including UPF1 and UPF2 factors that will cleave the targeted mRNAs.[2][3][4][5][6]

SMD occurs when staufen protein binds to an mRNA and recruits SMD factors (i.e. UPF1, UPF2) that degrade the RNA molecule bound to staufen. SMD potently affects metabolism because it is reported to involve gene expression in more than 1000 mRNA transcripts. SMD is reported to be a stepwise process: 1) two staufen protein particles bind target mRNA by their double-stranded RNA binding domain (dsRBD) 3 and 4, 2) the two staufen particles dimerizes by establishing non-covalent interactions between their staufen-swapping motif (SSM) and dsRBD5 located in their C' termini, 3) this dimerized staufen complex is recognized by SMD factors (i.e. UPF1, UPF2). It was reported that, upon SSM deletion, staufen particles bind to target mRNA but fail to dimerize and form a non-dimerized staufen complex. This complex inhibits SMD.[7]

References

  1. ↑ Lucas, Bronwyn A.; Lavi, Eitan; Shiue, Lily; Cho, Hana; Katzman, Sol; Miyoshi, Keita; Siomi, Mikiko C.; Carmel, Liran et al. (2018-01-30). "Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay". Proceedings of the National Academy of Sciences 115 (5): 968–973. doi:10.1073/pnas.1715531115. PMID 29339519. PMC 5798355. https://www.pnas.org/doi/full/10.1073/pnas.1715531115. 
  2. ↑ Gleghorn, Michael L.; Gong, Chenguang; Kielkopf, Clara L.; Maquat, Lynne E. (April 2013). "Staufen1 dimerizes through a conserved motif and a degenerate dsRNA-binding domain to promote mRNA decay" (in en). Nature Structural & Molecular Biology 20 (4): 515–524. doi:10.1038/nsmb.2528. ISSN 1545-9985. PMID 23524536. PMC 4096160. https://www.nature.com/articles/nsmb.2528. 
  3. ↑ Park, Eonyoung; Gleghorn, Michael L.; Maquat, Lynne E. (2013-01-08). "Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity" (in en). Proceedings of the National Academy of Sciences 110 (2): 405–412. doi:10.1073/pnas.1213508110. ISSN 0027-8424. PMID 23263869. PMC 3545820. https://pnas.org/doi/full/10.1073/pnas.1213508110. 
  4. ↑ Park, Eonyoung; Maquat, Lynne E. (2013). "Staufen-mediated mRNA decay" (in en). WIREs RNA 4 (4): 423–435. doi:10.1002/wrna.1168. ISSN 1757-7012. PMID 23681777. PMC 3711692. https://onlinelibrary.wiley.com/doi/abs/10.1002/wrna.1168. 
  5. ↑ Gowravaram, Manjeera; Schwarz, Juliane; Khilji, Sana K.; Urlaub, Henning; Chakrabarti, Sutapa (2019-11-07). "Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP" (in en). Nature Communications 10 (1): 5054. doi:10.1038/s41467-019-13080-x. ISSN 2041-1723. PMID 31699982. PMC 6838198. https://www.nature.com/articles/s41467-019-13080-x. 
  6. ↑ Kim, Yoon Ki; Furic, Luc; DesGroseillers, Luc; Maquat, Lynne E. (January 2005). "Mammalian Staufen1 Recruits Upf1 to Specific mRNA 3′UTRs so as to Elicit mRNA Decay". Cell 120 (2): 195–208. doi:10.1016/j.cell.2004.11.050. ISSN 0092-8674. https://linkinghub.elsevier.com/retrieve/pii/S0092867404011572. 
  7. ↑ Tripepi, Andrea; Shakoor, Huma; Zlobina, Maria; Klumpler, Tomáš; Kubíčková, Monika; Houser, Josef; Klapetek, Petr; Lukavsky, Peter Josef (2026). "Staufen-swapping motif is crucial for Staufen dimerization, structure, and Staufen-mediated mRNA decay" (in en). Protein Science 35 (7). doi:10.1002/pro.70669. ISSN 1469-896X. PMID 42300088. PMC 13270411. https://onlinelibrary.wiley.com/doi/abs/10.1002/pro.70669. 



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