Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and More »
Long non-coding RNAs (lncRNAs) are emerging as important regulatory molecules in developmental, physiological, and pathological processes. However, the precise mechanism More »
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MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures
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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]
Source – Centre for Genomic Regulation
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…)
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]
Long non-coding RNAs (lncRNAs) represent a class of potent regulators of gene expression that are found in a wide array of eukaryotes, however, our knowledge about these molecules in plants is still very limited. In particular, a number of model plant species still lack comprehensive datasets of lncRNAs and their annotations and very little is known about their biological roles. To meet these short-comings, researchers at the Adam Mickiewicz University created an online database of lncRNAs in ten model plant species. The lncRNAs were identified computationally using dozens of publicly available RNA-Seq libraries. Expression values, coding potential, sequence alignments as well as other types of data provide annotation for the identified lncRNAs. In order to better characterize them, the researchers investigated their potential roles in splicing modulation and deregulation of miRNA functions. The data are freely available for searching, browsing and downloading from an online database called CANTATAdb.
Availability – CANTATAdb is located at: http://cantata.amu.edu.pl, http://yeti.amu.edu.pl/CANTATA/
- Szcześniak MW, Rosikiewicz W, Makałowska I. (2015) CANTATAdb: a Collection of Plant Long Non-coding RNAs. Plant Cell Physiol [Epub ahead of print]. [article]
deepBase v2.0 – identification, expression, evolution and function of small RNAs, LncRNAs and circular RNAs from deep-sequencing data
Small non-coding RNAs (e.g. miRNAs) and long non-coding RNAs (e.g. lincRNAs and circRNAs) are emerging as key regulators of various cellular processes. However, only a very small fraction of these enigmatic RNAs have been well functionally characterized. In this study, we describe deepBase v2.0, an updated platform, to decode evolution, expression patterns and functions of diverse ncRNAs across 19 species. deepBase v2.0 has been updated to provide the most comprehensive collection of ncRNA-derived small RNAs generated from 588 sRNA-Seq datasets. Moreover, we developed a pipeline named lncSeeker to identify 176 680 high-confidence lncRNAs from 14 species. Temporal and spatial expression patterns of various ncRNAs were profiled. We identified approximately 24 280 primate-specific, 5193 rodent-specific lncRNAs, and 55 highly conserved lncRNA orthologs between human and zebrafish. We annotated 14 867 human circRNAs, 1260 of which are orthologous to mouse circRNAs. By combining expression profiles and functional genomic annotations, we developed lncFunction web-server to predict the function of lncRNAs based on protein-lncRNA co-expression networks. This study is expected to provide considerable resources to facilitate future experimental studies and to uncover ncRNA functions.
A system-level overview of the deepBase v2.0 core framework. A total of 558 small RNA datasets and 478 RNA-seq datasets were retrieved from NCBI GEO or SRA database. All the small and large noncoding RNAs were identified. The expression, evolution and functions of these ncRNAs were further analyzed. All the results generated by deepBase v2.0 were deposited in MySQL relational databases and displayed in the visual browser and web pages.
Availability – deepBase v2.0 is available at: http://biocenter.sysu.edu.cn/deepBase/
- Zheng LL, Li JH, Wu J, Sun WJ, Liu S, Wang ZL, Zhou H, Yang JH, Qu LH. (2015) deepBase v2.0: identification, expression, evolution and function of small RNAs, LncRNAs and circular RNAs from deep-sequencing data. Nucleic Acids Res [Epub ahead of print]. [article]
Thomas Cech “A Brief History of Noncoding RNAs: from Ribozymes to Epigenetic lncRNAs”
A. Alfred Taubman Medical Research Institute, Kahn Auditorium
Ann Arbor, Michigan