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Research Areas

Specialized ribosomes, Translational control, Ribosome profiling, RNA Biology

Research Interests

The ribosome – the cellular machine that translates information in mRNA templates into functional protein – is made up of ribosomal RNAs and about 80 ribosomal proteins. Despite the many components, ribosomes are typically seen as invariant entities. The conventional approach to studying translation has been to treat ribosome recruitment by auxiliary protein factors to mRNA templates as the end-point of translational regulation. However, there has been evidence indicating that the composition of ribosomal proteins in ribosomes can vary and that this in turn leads to distinct phenotypes. This phenomenon has been documented largely in yeast, plants, fruit flies, and zebrafish, but has not been well-studied in mammalian systems, even though many human disorders have been linked with the dysregulation of translation. In particular, there is a class of human genetic disorders known as ribosomopathies, in which mutations occurring in certain genes ultimately lead to impaired ribosome biogenesis and function. The most well-documented ribosomopathy to date is Diamond Blackfan Anemia – almost half of patients with this disorder have mutations mapping to ribosomal proteins, with as many as 25% mapping to a single ribosomal protein, RPS19, alone. We are interested in studying different aspects of translational control, especially specialized ribosomes, in different contexts. We use a combination of molecular biology and genomics-based techniques, such as ribosome profiling, to approach this question. Through studying another facet of translational regulatory mechanisms, we hope to gain a deeper understanding of translational control and uncover novel avenues towards therapeutics development.

 

Figure adapted from Guo, Biochem Soc Trans, 2018

Awards

2016  President’s Young Scientist Award
2014  L’Oréal Singapore For Women In Science National Fellowship

 

Selected Publications

1. Ang, Z., Koean, R.A.G., Er, J., Lee, L.T., Tam, J.K.C., Guo, H., Ding, J.L. (2019) Novel AU-rich proximal UTR sequences (APS) enhance CXCL8 synthesis upon the induction of rpS6 phosphorylation. PLoS Genetics 15:e1008077

2. Guo, H. (2018) Specialized ribosomes and the control of translation. Biochem Soc Trans 46:855-869.

3. Gu, H., Do, D.V., Liu, X., Xu, L, Wong, Y., Sheng, N., Tilaye, G.A., Yang, H., Guo, H., Fu, X.-Y. (2018) A Stat3 target Mettl8 regulates mouse ESCs differentiation via inhibiting JNK pathway. Stem Cell Reports 10:1807-1820.

4. Eichhorn, S.W.*, Guo, H.*, McGeary, S.E., Rodriguez-Mias, R.A., Shin, C., Baek, D., Hsu, S.-H., Ghoshal, K., Villén, J., Bartel, D.P. (2014) mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. Mol Cell56:104-115.
   *Equal contribution

5. Guo, J.U., Agarwal, V., Guo, H., Bartel, D.P. (2014) Expanded identification and characterization of mammalian circular RNAs. Genome Biol 15:409.

6. Guo, H., Ingolia, N.T., Weissman, J.S., Bartel, D.P. (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466:835-840.
   **Featured in Nature Reviews Genetics:
    Swami. (2010) Small RNAs: Targeting transcripts for destruction. Nat Rev Genet 11:672
   **Recommended by the Faculty of 1000

7. Okamura, K., Chung, W.-J., Ruby, J.G., Guo, H., Bartel, D.P., Lai, E.C. (2008) The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs. Nature 453:803-806.

8. McCaw, B.J., Chow, S.Y., Wong, E.S., Tan, K.L., Guo, H., Guy, G.R. (2005) Identification and characterization of mErk5-T, a novel Erk5/Bmk1 splice variant. Gene 345:183-190.