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John Rinn – Genomic Garbage Man (Photo credit: ChimpLearnGood)
DNA: One man’s trash is another man’s treasure, but there is no JUNK after all
Author: Demet Sag, PhD
One man’s trash is another man’s treasure, but there is no JUNK after all:
The JUNK has a meaning
Long non-coding RNAs recognized after transcriptome sequencing and studied more closely recently thanks to genomic tiling arrays, cDNA sequencing and RNA-Seq, which they have provided initial insights into the extent and depth of transcribed sequence across human and other genomes. How many are there in the genome? What are their mechanisms? How can we use them in molecular diagnostics and targeted therapies? How do they effect the function in a disease? Is it possible to modulate gene expression at the level of stem cell to redirect the cell differentiation? These are the main questions that we are looking for.
In early 90s actually first lincRNA was described, Xist. The main function was dosage compensation. Then in 2000s FANTOM consortium project changed the perspective on these long transcripts. Then they are called natural antisense transcripts (NATs), because very large number of these transcripts is overlapping with, and is transcribed in the antisense direction, to protein-coding genes. As a result of this study 11000 lincRNA discovered from full length cDNAs in mice. Later, yet another shift occur since these transcribed units are solely located in the introns or within “junk” DNA of protein-coding genes. Another independent study quantified that about 40% of protein-coding genes express NATs. Proven that there is nothing junk about DNA. Then, it was found that there are 8000 lincRNAs and among these 4000 are determined since they provide cell identity with multi-exogenic, polyadenylated, capped, ether in the cytoplasm or in the nucleus. However, even more recent studies show that there are about 20,000 lincRNAs. Furthermore, lincRNAs are classified under three distinct class: 1. Long-non-coding RNAs away from protein-coding genes, 2 NATs transcribed from the opposite strand of protein-coding genes, 3. Intronic lincRNAs expressed from within the introns of protein coding genes.
The human genome, categorized by function of each gene product, given both as number of genes and as percentage of all genes. (Photo credit: Wikipedia)
Their function is under study. However, keep in mind that they are redundant, so deleting or creating null mutations may or may not answer specific development questions. On the other hand, epigenetics, gene imprinting, and pathologies can be the best resource to identify their specific roles in biological functions and interactions. Distinct gene regulation either as a cis or trans element, gene imprinting, modulating alternative splicing, nuclear organization, determining a chromatin structure are under study. This will allow us to relate genome structure and function in health and disease better. Identification of their function during biological responses require a long way to be completed due to complexity since lincRNAs also regulate microRNAs. Regardless of many obstacles there is a progress. Disregulation of these lincRNA mainly observed in several cancer types, prostate, breast, hepatocellular carcinoma, colorectal, glioma and melanoma, possibly more. Most of the studies are done in vitro. However, there are many great model organism work as well, such as mice, zebra fish, and worm.
It was also not surprising that their regulation possibly under control of hormones based on circadian clock of our body. So better to sleep eight hour a day is not a cliché.
Next topic will include understanding of lincRNA mechanisms and epigenetics followed by lincRNAs during disease and cellular genesis.
… therapies in a variety of animal models and contributed to regulatory CMC and IND-enabling safety and toxicology studies for inclusion in … sequences sort a-cardiac and b-cytoplasmic actin messenger RNAs to different cytoplasmic compartments. J. Cell. Biol., …
… and posttranscriptional mechanisms contributing to the regulatory network. We examined proinflammatory gene regulation in … articles What about Circular RNAs? (pharmaceuticalintelligence.com) How Genes Function …
… due to their broad scope and non-specificity in the human genome. “I am extremely pro-patent, but I simply believe that people … believe that individuals have an innate right to their own genome, or to allow their doctor to look at that genome, just like the lungs or …
… Intelligence http://pharmaceuticalintelligence.com/2013/03/02/genome-sequenc…of-the-healthy/ Key Issues in Genome Sequencing of Healthy Individuals Eric Topol, MD, Genomic Medicine I … touching on important controversies in the use of whole genome …
… of recombination is highly uneven across the human genome, as in all studied organisms. Substantial recombination active regions … this variation would require comparison of recombination genome-wide among many single genomes. Whole-genome amplification (WGA) of …
… Lev-Ari, PhD, RN and Pnina G. Abir-Am, PhD Putting Genome Interpretation to the Test 01/30/2013 Ashley Yeager How well do methods for interpreting genome variation work? Ashley Yeager takes a look at a community experiment that is trying to assess just how useful genome interpretation tools in real-world situations. At the American …
… genomes — through the end of this year, National Human Genome Research Institute estimates indicate. And in his book, The Creative … the interpretation of an apparently healthy person’s genome and that of an individual who is already affected by a disease, whether …
… scary findings: the tale of John Lauerman’s whole genome sequencing FEBRUARY 15, 2012 Joe Thakuria draws John Lauerman’s blood for whole genome sequencing. By Madeleine Price Ball, licensed under … scary findings: the tale of John Lauerman’s whole genome sequencing » Joe Thakuria draws John …
… 2: LEADERS in the Competitive Space of Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in … Treatment http://pharmaceuticalintelligence.com/2013/01/13/leaders-in-genome-sequencing-of-genetic-mutations-for-therapeutic-drug-selection-in-cancer- …
Genome-Wide Detection of Single-Nucleotide and Copy-Number Variation of a Single … of DNA replication and the ability to amplify a whole genome. The amplicons are then sequenced either by whole-genome sequencing methods using Sanger-sequencing to verify any single …
… Aviva Lev-Ari, RN Genome Biol. 2012 Dec 13;13(12):R115. [Epub ahead of print] Whole-genome reconstruction and mutational signatures in gastric cancer. Nagarajan … read and DNA-PET sequencing to present the first whole-genome analysis of two gastric adenocarcinomas, one with chromosomal …
… by interpreting the mathematical patterns in the cancer genome. Researchers at the University of Oslo, Norway (UiO) have developed a … Hospital and UiO. Finds the changed patterns in the genome There is much talk about finding the special cancer gene. In reality, …
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I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
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I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
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Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
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Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
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Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
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Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
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Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette