Tag Archives: lncrna

DECKO – Single-oligo, dual-CRISPR deletion of genomic elements including long non-coding RNAs

lncRNA

For some time, scientists have been seeking a more efficient and reliable way to edit the genome and modify it to suit any need. A technique called CRISPR-Cas9 was recently launched as the solution to this problem, and has since taken a position as one of the most revolutionary techniques in molecular biology.

Although CRISPR-Cas9 is much more powerful than previous genome editing methods, it still has certain limitations. For example, it is very useful when dealing with genome fragments that code for proteins but, in reality, this covers just 1% of the genome. The remaining 99%, the “dark matter”, or what was once known as “junk DNA” still could not benefit from the advantages offered by this revolutionary technique.

Now, researchers at the Centre for Genomic Regulation, led by Rory Johnson, are presenting a new method that makes it possible to use the CRISPR-Cas9 technique on DNA dark matter, too. The method has been presented in an article published in BMC Genomics and is available on an open-access basis for the entire scientific community.

The method we’re proposing expands the use of CRISPR to the DNA dark matter. Broadening the use to the whole genome takes this technique to a new level and allows us to simultaneously explore and edit certain genes that often have regulating functions, more efficiently and economically,” say Rory Johnson and Estel Aparicio, the CRG researchers who authored the study. “This will be extremely useful in studies where the goal is to examine the functions of genes located in the dark area (called “long non-coding RNA’s”) and not only will we be able to “activate” or “deactivate” one gene at a time, we will also be able to manipulate thousands ofdifferent genes at the same time,” state Johnson and Aparicio.

Much hope has been deposited in the CRISPR technique, and it is now being used in laboratories around the world. Although still being used at a very basic experimental level, it is thought that in the long term it will have major applications not only in the realm of biomedicine to design customized or new cells or treatments, but also for biofuels or agriculture. Thanks to the CRG researchers’ proposal, this technique offers even greater possibilities. “We will finally have a method that allows us to easily cut, paste and edit the genome at every level,” adds Roderic Guigó, coordinator of the CRG Bioinformatics and Genomics programme. “Being able to perform broad-scale experiments and explore this ‘dark’ region will allow us to advance a great deal in the knowledge of gene expression regulation and therefore, delve further into how to manage the information that makes our cells, organs and tissues as they are and function correctly.

The new methodology will be the basis on which to explore all of the information now available thanks to the projects related with the human genome, and that make genomic data available to researchers. “The ‘cut and paste’ technique will take us from simply reading the genome to understanding its functions and therefore, being able to have an impact on the disease,” concludes Dr Johnson.

  • Aparicio-Prat E, Arnan C, Sala I, Bosch N, Guigó R, Johnson R. (2015) DECKO: Single-oligo, dual-CRISPR deletion of genomic elements including long non-coding RNAs. BMC Genomics 16:846. [article]

SourceCentre for Genomic Regulation

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Long noncoding RNAs in lung cancer – what we know in 2015

lncRNA

Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains extremely low. Long noncoding RNAs (lncRNAs), which lacking protein-coding ability, have recently emerged as pivotal participants in biological processes, often dysregulated in a range of cancers, including lung cancer. While our understanding of lncRNAs in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the activities of lncRNAs will certainly secure strong biomarkers and improve treatment options for lung cancer patients. (read more…)

lncRNA

The locations and characteristics of lncRNA

  • Xu YJ, Du Y, Fan Y. (2015) Long noncoding RNAs in lung cancer: what we know in 2015. Clin Transl Oncol [Epub ahead of print]. [abstract]

Symbiosis with Ancient Viruses Critical for Human Development

from Bioscience Technology by Cynthia Fox

lncRNA

Human blastocysts don’t develop when ancient virus RNA, “trapped” in our DNA for millions of years, is artificially blocked.

In recent years humans have come to understand we are not just about Darwinian natural selection, but symbiosis. For two billion years, there were only bacteria and archaea. Then a single archaea swallowed a bacteria in such a way the bacteria became its powerpack. Complex life exploded out of this symbiosis.

Remnants of that moment are alive in humans today: experimental and genetic analysis proves the power packs of our cells, mitochondria, are indeed ancestors of those ancient bacteria.

This week a Stanford University crew reported in Nature Genetics making another key symbiosis finding: human embryos need ancient viral RNA, trapped in the non-protein-coding regions of our genomes, to grow. They are essential for our existence.

Those ancient viral RNA “were acquired in the primate lineage, some millions of years ago, by infection/insertion into the germ-cell lineage that gives rise to eggs and sperm,” developmental biologist Renee Reijo Pera, Ph.D., told Bioscience Technology. Reijo Pera, co-senior author on the study, is now vice president for research and economic development at Montana State University. “Our development without them would have been fundamentally different.  Different species likely all use their own sequences. To the best of our knowledge, there are no other data to show that single non-coding, human-specific, retrovirally derived genes are essential for timing or cell fate decisions in human development. We were very surprised by the results.”

Harvard University/Massachusetts Institute of Technology geneticist John Rinn, Ph.D., told Bioscience Technology that function was earlier linked to some retroviral RNA elements found in isolated stem cells, and induced pluripotency. But he agreed that, until now, a seminal role was not found for those elements in actual human development: “This manuscript makes significant progress in understanding the functional roles of ERV-lncRNA [endogenous retroviral long-coding RNA].” Rinn was uninvolved in the work.

“The paper is interesting because it is one of the first to probe the role of long non-coding RNA— a relatively poorly understood class of regulatory RNAs— in early human development and pluripotency,” Harvard stem cell researcher George Daley, M.D., Ph.D., told Bioscience Technology. Daley, director of the Dana Farber Cancer Institute/Boston Children’s Hospital Stem Cell Transplantation Program, made some early lncRNA finds with Rinn. He was also uninvolved in the new work.

(read more…)

Post-transcriptional regulation of long noncoding RNAs in cancer

It is a great surprise that the genomes of mammals and other eukaryotes harbor many thousands of long noncoding RNAs (lncRNAs). Although these long noncoding transcripts were once considered to be simply transcriptional noise or cloning artifacts, multiple studies have suggested that lncRNAs are emerging as new players in diverse human diseases, especially in cancer, and that the molecular mechanisms of lncRNAs need to be elucidated.

lncRNA

More recently, evidence has begun to accumulate describing the complex post-transcriptional regulation in which lncRNAs are involved. It was reported that lncRNAs can be implicated in degradation, translation, pre-messenger RNA (mRNA) splicing, and protein activities and even as microRNAs (miRNAs) sponges in both a sequence-dependent and sequence-independent manner. In this review, the authors present an updated vision of lncRNAs and summarize the mechanism of post-transcriptional regulation by lncRNAs, providing new insight into the functional cellular roles that they may play in human diseases, with a particular focus on cancers.

  • Shi X, Sun M, Wu Y, Yao Y, Liu H, Wu G, Yuan D, Song Y. (2015) Post-transcriptional regulation of long noncoding RNAs in cancer. Tumour Biol [Epub ahead of print]. [abstract]

Community Curated Database For LncRNA

lncRNA

A wiki-style database hopes to serve as an online encyclopedia of lncRNA by and for the scientific community.

Scientists have set up a long non-coding RNA (lncRNA) database aimed at harnessing the collective knowledge of the scientific community. This study has been published in Nucleic Acids Research.

LncRNAs are RNAs that do not code for proteins but are nonetheless actively transcribed in human genome. In recent years, it has been recognized that they perform significant roles in a large variety of biological processes. The dysregulation of lncRNA expression is highly correlated with human cancer, neurological disorders, and many other human diseases.



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