Decodificada a linguagem do RNA: nova função para os pseudogenes e RNAs não codificantes

Language of RNA Decoded: Study Reveals New Function for Pseudogenes and Noncoding RNAs

ScienceDaily (June 24, 2010) — The central dogma of molecular biology, as proposed in 1970 by Francis Crick and James Watson, holds that genetic information is transferred from DNA to functional proteins by way of messenger RNA (mRNA). This suggests that mRNA has but a single role, that being to encode for proteins.

Now, a cancer genetics team at Beth Israel Deaconess Medical Center (BIDMC) suggests there is much more to RNA than meets the eye.

In a study appearing in the June 24, 2010 issue of Nature, the authors describe a new regulatory role for RNA -- independent of their protein-coding function -- that relies on their ability to communicate with one another. Of potentially even greater significance, because this new function also holds true for thousands of noncoding RNAs, the discovery dramatically increases the known pool of functional genetic information.

The new findings suggest that nature has crafted a clever tale of espionage such that thousands upon thousands of mRNAs and noncoding RNAs, together with a mysterious group of genetic relics known as pseudogenes, take part in undercover reconnaissance of cellular microRNAs, resulting in a new category of genetic elements which, when mutated, can have consequences for cancer and human disease at large.

"Because this new function does not depend on the blueprint that RNAs harbor in their protein-encoding nucleotide sequence, the discovery additionally holds true for the thousands of noncoding RNA molecules in the cell," explains senior author Pier Paolo Pandolfi, MD, PhD, Director of Research at the BIDMC Cancer Center and George C. Reisman Professor of Medicine at Harvard Medical School."This means that not only have we discovered a new language for mRNA, but we have also translated the previously unknown language of up to 17,000 pseudogenes and at least 10,000 long non-coding (lnc) RNAs. Consequently, we now know the function of an estimated 30,000 new entities, offering a novel dimension by which cellular and tumor biology can be regulated, and effectively doubling the size of the functional genome."

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Read more here/Leia mais aqui: Science Daily

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FREE PDFS GRÁTIS

1. Decoy for microRNAs 

Pseudogenes are considered to be defunct relatives of known genes. But there is some surprising news:

pseudogenes are functional and could have a role in the control of cancer1. Two experts discuss the

significance of these findings for understanding the regulation of gene expression and cancer biology.

2. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

Laura Poliseno, Leonardo Salmena, Jiangwen Zhang, Brett Carver, William J. Haveman & Pier Paolo Pandolfi

Affiliations
Contributions
Corresponding authorNature 465, 1033–1038 (24 June 2010) doi:10.1038/nature09144Received 21 September 2009 Accepted 22 April 2010

Abstract

The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.

Subject terms: Cancer   Molecular biology   Cell biology   Genetics    Genomics

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