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Control of Gene Expression

 

 

Research Interests

It is important to study RNA metabolism in different systems, to allow universally conserved features to be recognized. Future work will involve the identification and study of the mechanism of action of more RNases, relating these RNases to RNA decay through the isolation of mutants, and assessing whether the various reactions are  regulated. Taking this into account our research objectives are:

- Post-Transcriptional Control of Gene Expression
- Mechanism and Control of mRNA degradation.
- Characterization and Study of ribonucleases in the control of RNA Decay.
- Metabolism of the Poly(A) tail in Bacterial mRNAs
- Post-Transcriptional Studies in Escherichia coli Focusing on the Control of Cell Division
- Control of gene expression under stress and stationary phase.
- RNA processing in Lactic Acid Bacteria
- Small RNAs and Control of Gene Expression

Ribonuclease II is a key exonuclease involved in the maturation, turnover and quality control of RNA. RNase II-family is ubiquitous in nature and mutations have been linked with abnormal chloroplast biogenesis, mitotic control and cancer. In eukaryotes, these enzymes are found in the ribonuclease complex called the exosome. In 2006 we have performed structural and functional studies on Escherichia coli RNase II and have characterized a mutant protein. In collaboration with the crystallography group of ITQB we have unravelled the dynamics of RNA degradation by RNase II and its RNA-bound complex.
A 3-dimensional model explaining the activity of these enzymes can now be proposed, opening an exciting new chapter in the comprehension of RNA maturation, selection and degradation, processes that ultimately control gene expression. This year we have also shown that Escherichia coli RNase R, a member of the RNase II family, can be very important in stationary phase. In addition we showed that Poly (A)-polymerase I links transcription with mRNA degradation via sigmaS proteolysis. This unexpected finding makes important connections and extends the research on RNA degradation to other important fields.

 

Group Members

  • Mónica Amblar, Post-doc
  • Patrick Freire, Post-doc
  • Sandra Viegas, PhD student
  • Ana Barbas, PhD student
  • José Andrade, PhD student
  • Inês Guinote, PhD student
  • Ana Furtado, Master Student
  • Francisco Mesquita, Master Student
  • Margarida Matos, Master Student
  • Rute Matos, Master Student
  • Inês Heinrichson, Undergraduate

 

 

Selected Publications

  1. Frazão C, McVey CE, Amblar M, Barbas A, Vonrhein C, Arraiano CM, Carrondo MA (2006). Unravelling the dynamics of RNA degradation by ribonuclease II and its RNA-bound complex. Nature. 443(7107):110-4.
  2. Andrade JM, Cairrão F, Arraiano CM (2006). RNase R affects gene expression in stationary phase: regulation of ompA. Mol Microbiol. 60:219-28.
  3. Santos JM, Freire P, Mesquita FS, Mika F, Hengge R, Arraiano CM (2006). Poly(A)-polymerase I links transcription with mRNA degradation via sigmaS proteolysis. Mol Microbiol. 60:177-88.

 

 

Laboratory's Webpage

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Controlo da Expressão Génica (PT)

Muitos processos biológicos não podem ser compreendidos sem se conhecer detalhadamente o metabolismo do RNA. A contínua degradação e síntese de RNA possibilita a rápida produção de novas proteínas e permite que os organismos se adaptem ao seu ambiente. Desta forma os níveis do RNA podem regular a síntese de proteínas e o crescimento celular. Se pudermos estabilizar em cada célula o número de moléculas de RNA que codificam uma proteína de interesse, então a produção pode ser alterada para uma vasta gama de aplicações de importância biomédica e farmacêutica. O nosso laboratório estuda o papel da maturação e degradação do RNA na regulação da expressão génica. Nos últimos anos a investigação sobre RNA tem sido designada uma das maiores prioridades científicas pois descobriram-se novos tipos de RNA em cada organismo e viu-se que através do RNA se podem curar doenças e até modificar o património genético. Como tal estamos a estudar a acção de ribonucleases (enzimas que degradam o RNA) e, em colaboração com parceros internacionais, empregamos tecnologias avançadas como o uso de RNomics (estudo de pequenos RNAs não codificantes) para continuar a dar o nosso contributo para o conhecimento deste mecanismo regulador da expressão génica. 

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