STOP-codon dysfunction & Translation control

Background

We have previously shown the role of STOP-codon mutations (nonSTOP mutations) in cancer progression by inactivating tumor suppressors like SMAD4. In addition, there are naturally leaky STOP codons which leads to translation across them, allowing synthesis of proteins with variable C-terminus. This is termed "stop-codon readthrough". We are interested in understanding the mechanisms and consequences of both genetic mutations and readthrough in physiology and cancer. In addition, we also investigate the role of transcript-specific translational control mechanisms.

References

• Brar GA. Beyond the Triplet Code: Context Cues Transform Translation. Cell. 2016 Dec 15;167(7):1681-1692.

• Dhamija S, Yang CM, Seiler J, Myacheva K, Caudron-Herger M, Wieland A, Abdelkarim M, Sharma Y, Riester M, Groß M, Maurer J & Diederichs S (2020). A pan-cancer analysis reveals nonstop extension mutations causing SMAD4 tumor suppressor degradation. Nat Cell Biol, 22: 999-101

• Tiedje, C, Ronkina, N, Tehrani, M, Dhamija, S, Laass K, Holtmann H, Kotlyarov A & Gaestel M (2012) The p38/MK2-driven exchange between tristetraprolin and HuR regulates AU-rich element-dependent translation. PLoS Genet 8: e1002977           

• Dhamija S, Kuehne N, Winzen R, Doerrie A, Dittrich-Breiholz O, Thakur BK, Kracht M & Holtmann H (2011) Interleukin-1 activates synthesis of interleukin-6 by interfering with a KSRP-dependent translational silencing mechanism. J Biol Chem 286: 33279-33288.  

• Dhamija S, Doerrie A, Winzen R, Dittrich-Breiholz O, Taghipour A, Kuehne N, Kracht M & Holtmann H (2010) IL-1-induced post-transcriptional mechanisms target overlapping translational silencing and destabilizing elements in IκBzeta mRNA.J Biol Chem 285: 29165-29178.

• Book Chapter: Dhamija S & Menon MB. Long non-coding RNAs as scaffolds for multiprotein signalling complexes (2020). In  “RNA Technologies” Springer Series Vol. 10: The Chemical Biology of Long Noncoding RNAs, 10: 131-147.