Missing Lincs - Science News - 6 views
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Nitchakan Chaiprukmalakan on 01 Apr 12Scientists are finding more information about the importance of the non coding RNAs, lincRNAs.
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Only now have scientists begun identifying the previously invisible cOntractors who make sure that materials get where they are supposed to be and in the right order to build a human being or any other creature. Some of these little-known workers belOng to a class of molecules called lOng intergenic nOncoding RNAs.
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And the lincRNAs originate in what scientists used to view as barren wastelands between protein-coding genes. But new research is showing that these formerly underappreciated workers have important roles in projects both large and microscopic.
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In the last few years, scientists have learned that lincRNAs, as well as other RNAs that are long and noncoding but not intergenic, perform a variety of jobs. Some serve as guides showing proteins where to go, while others tether proteins to different types of RNA, or to DNA. Some work as decoys, distracting regulatory molecules from their usual assignments. Some may even have multiple roles, all the while chattering away to other RNA within cells. (It is not idle gossip; RNA communication within cells may ward off diseases such as cancer.) And as the ultimate multitaskers, lincRNAs keep proper cellular development ticking along and help define what makes mice mice and people people.
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That archive contains about 3 billion genetic letters, far more than the genomes of less complex organisms such as roundworms and fruit flies.
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In 2005, the research revealed that even though genes that code for proteins make up only 1.5 percent of the mouse genome, more than 63 percent of the genome’s DNA is copied into RNA. In humans the number is even higher, with up to 93 percent of the genome made into RNA, even though protein-coding genes make up less than 2 percent of the genome.
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At first, many scientists didn’t know what to make of the excess RNA. Some thought it was overexuberance on the part of the DNA-copying machinery. But gradually researchers began to realize that many of those extra RNAs had important jobs to do.
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Some, though, appear to act like general contractors — not hammering in the nails and pouring the foundations of cells themselves, but dictating how the job should be done.
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One of the most famous lOng nOncoding RNAs, known as XIST, is also One of the most hands-On. XIST is in charge of shutting down One of the X chromosomes in every single cell of women and girls
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XIST doesn’t have a long commute to work; it coats whichever X chromosome makes it, preventing other genes on the chromosome from being activated
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One of the most well-studied lincRNAs, named HOTAIR, wasn’t lucky enough to get a job close to home. It is copied from DNA On chromosome 12 but has to travel to chromosome 2 to shut down several genes in a group known as the HOXD cluster, genes important for proper development of an organism
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Not only does HOTAIR help direct development, but it is also important throughout life to help cells pinpoint their location in the body.
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A lincRNA known as HOTTIP also works with a crew of histone modifiers, but instead of shuttering genes, HOTTIP’s crews hang grand-opening signs to attract gene-activating machinery
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In the recipe for humans, lincRNAs are in the thick of things from the very beginning. At least 26 different lincRNAs need to be on to keep an embryonic stem cell a stem cell
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Just how lincRNAs choose which genes to turn on and off isn’t yet known. But Pier Paolo Pandolfi, a geneticist at Beth Israel Deaconess and Harvard Medical School, suspects that the lincRNAs are whispering to each other and to other RNAs, keeping tabs on all a cell’s goings-on. Pandolfi laid out his hypothesis for how this chatter might help control protein production and other processes in the Aug. 5 Cell.
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The Columbia team and Pandolfi’s team independently found that tweaking levels of a few messenger RNAs that distract microRNAs from PTEN messenger RNA can lead to prostate cancer or a type of brain tumor called glioblastoma. Just messing with levels of a messenger RNA from another gene known as ZEB2 throws off PTEN protein levels and can lead to melanoma in mice, Pandolfi’s group reported in another paper in the Oct. 14 Cell.
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Losing one noncoding RNA may be disastrous for a cell, but for want of noncoding RNAs whole species may never have evolved, argues Queensland’s Mattick. He and others say the real function of lincRNAs is to give evolution a sort of molecular clay from which to mold new designs.
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Humans have several lincRNAs that are found in no other species. Many of those RNAs are made in the brain, leading scientists to speculate that the molecules may be at least partially responsible for that important organ’s evolution.