Monthly Archives: June 2013

June 16, 2013 Because of their central importance to biology, proteins have been the focus of intense research, particularly the manner in which they are produced from genetically coded templates -- a process commonly known as translation. While the general mechanism of translation has been understood for some time, protein synthesis can initiate by more than one mechanism. One of the least well understood mechanisms is known as cap-independent translation.

Now, John Chaput and his colleagues at Arizona State University's Biodesign Institute have produced the first genome-wide investigation of cap-independent translation, identifying thousands of mRNA sequences that act as Translation Enhancing Elements (TEEs), which are RNA sequences upstream of the coding region that help recruit the ribosome to the translation start site.

The new study outlines a technique for mining whole genomes for sequences that initiate cap-independent translation within the vastness of the genome.

The research has important implications for the fundamental understanding of translation in living systems, as well as intriguing potential in the biomedical arena. (Many viral pathogens are known to use cap-independent translation to hijack and redirect cellular mechanisms to translate viral proteins.)

The lead author of the study is Brian P. Wellensiek, a senior scientist in Biodesign's Center for Evolutionary Medicine and Informatics. The group's results appear in the current issue of the journal Nature Methods.

During most protein synthesis in eukaryotic cells, cap-dependent translation dominates. The process begins after DNA is first transcribed into mRNA, with the aid of an enzyme polymerase. mRNA now forms the coded template from which the translated proteins will be generated. The mRNA code consists of sequences made from 4 nucleic acids, A, C, G & U, with each 3-letter grouping (known as a codon), corresponding to one amino acid in the protein being synthesized.

A key component in the translation process is the ribosome, which migrates along the single stranded mRNA, reading the codons as it goes. Before it can do this however, it must locate a special structure at the 5' end of the mRNA strand known as the cap. In normal cap-dependent translation, the ribosome is recruited to the 5' end of mRNA via a specialized cap-binding complex.

Cap-independent translation allows the ribosome to begin reading the mRNA message without having to first locate the 5' cap structure. Cap-independent translation occurs in eukaryotic cells during normal processes including mitosis and apoptosis (or programmed cell death). It is also a feature in many forms of viral translation, where the viral transcript is able to recruit the ribosome and co-opt its function to preferentially translate viral RNA.

In the current study, Chaput designed an in vitro selection strategy to identify human genome sequences that initiate cap-independent translation. The technique is able to select candidates from a pool of trillions of genomic fragments. Once a set of sequences was identified as translation enhancing elements, they were shown to function effectively in both cell-free and cellular translation systems.

As Chaput explains, most research on cap-independent translation has been conducted using RNA fragments derived from viruses. "These RNA molecules will fold into shapes that appear to mimic some of the initiation factors that that you would find in eukaryotic translation," he says. More recently, similar RNA molecules have been identified in cellular systems, though the sequences tend to be much shorter and function in a different manner.

Originally posted here:
Mapping translation sites in the human genome

WASHINGTON, DC.- The Smithsonians National Museum of Natural History, in partnership with the National Human Genome Research Institute of the National Institutes of Health, opened Genome: Unlocking Lifes Code June 14a multimedia exhibition that explores how the genomic revolution is influencing peoples lives and the extraordinary impact it is having on science, medicine and nature.

The exhibition looks at the complexities of the genomethe complete set of genetic or hereditary material of a living organismand chronicles the remarkable breakthroughs that have taken place since the completion of the Human Genome Project 10 years ago. With cutting-edge interactives, 3-D models, custom animation and engaging videos of real-life stories, the exhibition examines both the benefits and the challenges that genomics presents to modern society.

Genome: Unlocking Lifes Code is on view at the National Museum of Natural History through Sept. 1, 2014, when it will begin a tour of venues throughout North America.

Genomic research is a vital tool for exploring the mysteries of the natural world, and it is an important part of Smithsonian science, said Kirk Johnson, the Sant Director of the National Museum of Natural History.

Genome: Unlocking Lifes Code will help our visitors understand how genomics is transforming what we know about ourselves and how we make important life decisions.

Genome: Unlocking Lifes Code celebrates the anniversaries of two landmark scientific discoveries: the 10th anniversary of the Human Genome Projects first completely sequenced human genome and the 60th anniversary of James Watson and Francis Cricks discovery of DNAs double helix structure.

This exhibition reflects a remarkably productive collaboration between two scientific icons of the U.S. governmentthe Smithsonian Institution and the National Institutes of Health, said Dr. Eric D. Green, director of the National Human Genome Research Institute, one of the 27 institutes and centers that make up NIH in Bethesda. Our ability to share the science of genomics with the more than 7 million annual visitors to the National Museum of Natural History is profoundly exciting for the broader genomics research community.

When visitors enter the 4,400-square-foot exhibition they will be immersed in an interactive environment that communicates the pervasiveness of genomic science and provides new ways of looking at themselvesas individuals, as members of a family and a species, and as part of the diversity of all life.

Genome: Unlocking Lifes Code is organized around four themed areas, offering visitors personalized and interactive experiences that examine what a genome is (The Genome Within Us), how it is related to medicine and health (Your Genome, Your Health), how it connects them to all of life (Connections: Natural World and Genomic Journey) and how it is a part of their own personal story (Genome Zone):

The Genome Within UsAt the center of the exhibition, museumgoers will explore how the genome is a part of their own bodies. They will discover what a genome is, where it is located in the human body (in the cell nucleus), why it matters and how it influences life, all through introductory videos produced by the History channel. Visitors will see three-dimensional models of a human genome and watch historic interviews with Human Genome Project researchers. They can also participate in a media interactive that explores the ethical, legal and social implications of advancing DNA sequencing technologies and submit their responses on an interactive station and find out how their views compare with those of other visitors. An electronic news-ticker display will provide an ongoing stream of recent developments in genomics.

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National Museum of Natural History genome exhibition unlocks 21st-century science of life

The $14.5 billion U.S. investment in the Human Genome Project, completed a decade ago, has paid off more than 60-fold in new jobs, drugs and a rapidly expanding genetics industry, an analysis has found.

The endeavor to map human DNA in its entirety created $966 billion in economic impact and $59 billion in federal tax revenue, according to the study released last week by United for Medical Research and Battelle, two research advocacy groups.

Dozens of companies have started with the knowledge gained from the project, leading to new diagnostic tests and development of medicines that can be matched with gene variants linked to disease. The project triggered a new era in the life sciences, with new oncology drugs and screenings among the early developments in the field, said Greg Lucier, chief executive officer of Life Technologies.

Up until that time, the pharmaceutical industry was able to have major impact on human health through blockbuster drugs that in retrospect were relatively simple, he said in a telephone interview. The ushering in of the genomic era was the beginning of truly reducing science to engineering, in terms of the understanding of life.

Life Technologies also provided funding for the study. The Carlsbad, Calif.-based maker of gene-sequencing machines agreed to be bought by Thermo Fisher Scientific for $13.6 billion last April. Other companies that provide sequencing services or equipment include Illumina and Oxford Nanopore Technologies. The Human Genome Project also spurred consumer-focused genetics companies such as 23andMe that let people find out what diseases they might be at risk for or where their ancestry lies.

Although it took almost $15 billion and more than a decade for the government-funded DNA effort to fully sequence a human genome for the first time, companies can now sequence a whole genome for about $1,000 and do it in a day.

The Human Genome Project was the starting point of that magnificent, incredible effort, Lucier said.

The market for gene tests may expand to $25 billion from $5 billion within a decade as more doctors use a patients genetic makeup to tailor treatments, according to a report last year from UnitedHealth Group Inc., the largest U.S. health insurer.

This report illustrates the vital role that key federal research funding plays in growing the U.S. economy, creating new industries and innovative technologies and producing the diagnostics and treatments that can save lives, Carrie Wolinetz, president of United for Medical Research, said in a statement.

Some of biggest innovations have been in the field of oncology. The actress Angelina Jolie recently became the new face of breast cancer, after announcing that shed had a double-mastectomy upon discovering that she carried a gene that predicts about a 60 percent chance of developing the disease.

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Genome project spurs boom for life science