Researchers Explore Additional Coding Potential Hidden in the Human Genome

Sequencing the human genome was just the first step. The next challenge is of the kind that makes history: to decode the genome, and understand how the information needed to construct a human being can be packaged into a single molecule. And there are a lot more than loose ends in the way of a solution. A group of bioinformatics experts at the Spanish National Cancer Research Centre (CNIO) in Madrid have published findings which point to still unexplored coding potential within the genome.

The substance responsible is chimeric RNA, formed not from one gene but from fragments of several. "There is growing evidence, some of it very recent, that genome coding is more complicated than we thought, and that some RNAs may combine information from two distinct genes," explains Alfonso Valencia, head of the CNIO's Structural Biology and Biocomputing Program. "We have called them chimeric RNAs after the mythological beings made from the parts of two different animals," he relates.

The research has been carried out in collaboration with scientists from the Centro de Regulación Genómica (CRG) in Barcelona. "We noted the prevalence of this phenomenon back in 2006, and are now working to establish its biological importance," remarks Roderic Guigó, coordinator of the CRG's Bioinformatics and Genomics program.

DNA contains the genes, which are translated into proteins. RNA, meantime, serves as an intermediary molecule performing what is an indispensable step in the process: before a gene can be translated into a protein, the right RNA has to be built. The classical vision of how information is stored in the genome holds that the correspondence is one-to-one, that is: one gene, one RNA, one protein.

A paradigm shift needed
And that was what scientists expected to find when they sequenced the genome at the start of the last decade. But it was quickly apparent that there was a problem: the human genome contains some 20,000 genes, while the variety of proteins in the human body is considerably greater. Something was wrong.

We now know that a single gene can produce several proteins; just as a words like "bat", "foot" or "count" can have different meanings despite being written the same way. But it remains to be seen whether this is a common phenomenon - whether all genes can code for multiple proteins – or a rarity. In fact, here too Valencia's group has made advances, demonstrating in a paper published last April in Molecular Evolution Biology that the translation of a single gene into several proteins occurs, but is fairly uncommon.

Chimeric RNA is also partly responsible for there being more distinct proteins than there are genes. As if the system reading and translating the genes could find three or more meanings from any two. So, for example, "love" and "cast" would be direct translations, but we would also get "ve-st"; "ca-ve"; "lo-st"...

The existence of chimeric RNA was already an established fact, and it was also known that some chimeric RNAs are translated into proteins, while others remain in the RNA phase, as happens with normal, non-chimeric RNA. But chimeric proteins were generally believed to be a rarity confined to pathological processes like the development of cancer.

The CNIO's bioinformatics team trawled through gene, RNA and protein databases and conducted new experiments before finally discovering that chimeric RNA is present in far greater quantities than was first thought. They have also detected cases of translation to proteins as part of an apparently normal process in healthy as well as cancerous tissue.

Their results have been written up in a series of papers, the latest of which has just appeared in Genome Research (Frenkel-Morgenstern et al, 2012, PMID: 22588898) signed as first author by Milana Frenkel-Morgenstern, from the CNIO Structural Computational Biology Group that Valencia leads. The interest has been such that another journal, Nature Reviews Genetics, dedicated a commentary to the article (Post transcriptional regulation: Chimeric protein production, NRG, June 7, 2012, 10.1038/nrg3268).

Specifically, the CNIO researchers have identified 175 chimeric RNA transcripts in 16 human tissues, and 12 new chimeric proteins. This finding poses numerous questions: How important is this process out of all the information in the genome? Does it finally explain the mismatch between the number of genes and proteins? What is the total number of chimeric proteins? Is there some function that characterises them? Why do they exist?

"We have opened up a line of inquiry which we hope other groups will now pursue," remarks Valencia. "In my opinion, the key thing about this research is that it shows we still have a lot to learn before we fully understand what is written in the genome."

Most Popular Now

Giving Doctors an AI-Powered Head Start …

Detection of melanoma and a range of other skin diseases will be faster and more accurate with a new artificial intelligence (AI) powered tool that analyses multiple imaging types simultaneously...

Philips Foundation 2024 Annual Report: E…

Marking its tenth anniversary, Philips Foundation released its 2024 Annual Report, highlighting a year in which the Philips Foundation helped provide access to quality healthcare for 46.5 million people around...

Scientists Argue for More FDA Oversight …

An agile, transparent, and ethics-driven oversight system is needed for the U.S. Food and Drug Administration (FDA) to balance innovation with patient safety when it comes to artificial intelligence-driven medical...

AI Agents for Oncology

Clinical decision-making in oncology is challenging and requires the analysis of various data types - from medical imaging and genetic information to patient records and treatment guidelines. To effectively support...

Start-ups in the Spotlight at MEDICA 202…

17 - 20 November 2025, Düsseldorf, Germany. MEDICA, the leading international trade fair and platform for healthcare innovations, will once again confirm its position as the world's number one hotspot for...

AI Medical Receptionist Modernizing Doct…

A virtual medical receptionist named "Cassie," developed through research at Texas A&M University, is transforming the way patients interact with health care providers. Cassie is a digital-human assistant created by Humanate...

Using Data and AI to Create Better Healt…

Academic medical centers could transform patient care by adopting principles from learning health systems principles, according to researchers from Weill Cornell Medicine and the University of California, San Diego. In...

AI Tool Set to Transform Characterisatio…

A multinational team of researchers, co-led by the Garvan Institute of Medical Research, has developed and tested a new AI tool to better characterise the diversity of individual cells within...

AI Detects Hidden Heart Disease Using Ex…

Mass General Brigham researchers have developed a new AI tool in collaboration with the United States Department of Veterans Affairs (VA) to probe through previously collected CT scans and identify...

Highland Marketing Announced as Official…

Highland Marketing has been named, for the second year running, the official communications partner for HETT Show 2025, the UK's leading digital health conference and exhibition. Taking place 7-8 October...

Human-AI Collectives Make the Most Accur…

Diagnostic errors are among the most serious problems in everyday medical practice. AI systems - especially large language models (LLMs) like ChatGPT-4, Gemini, or Claude 3 - offer new ways...

MHP-Net: A Revolutionary AI Model for Ac…

Liver cancer is the sixth most common cancer globally and a leading cause of cancer-related deaths. Accurate segmentation of liver tumors is a crucial step for the management of the...