{"id":13329,"date":"2019-11-04T08:58:48","date_gmt":"2019-11-04T13:58:48","guid":{"rendered":"https:\/\/biology.mit.edu\/?p=13329"},"modified":"2020-10-28T22:33:01","modified_gmt":"2020-10-29T02:33:01","slug":"micrornas-work-together-to-tune-gene-expression-in-the-brain","status":"publish","type":"post","link":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/","title":{"rendered":"MicroRNAs work together to tune gene expression in the brain"},"content":{"rendered":"

A new study from the MIT Department of Biology suggests we may need to re-think how certain RNAs operate to impact development and disease.<\/p>\n

According to the \u201ccentral dogma\u201d of biology, DNA is converted into messenger RNA (mRNA) before being expressed as a protein. However, not all RNAs are destined to become proteins. MicroRNAs (miRNAs) are small, non-coding RNAs, which regulate a variety of cellular processes by binding to mRNAs and destabilizing them to reduce their expression.<\/p>\n

A single miRNA can target hundreds of different mRNAs. And yet, on its own, an individual miRNA only represses the expression of each mRNA target by about 10-20%. Given that the effects of a single miRNA are so mild, researchers couldn\u2019t understand how they could exert such powerful control over so many processes. One theory is that, rather than acting alone, perhaps multiple miRNAs bind to the same target mRNA in concert to exert enhanced repression. However, few studies have explored this idea in-depth, or identified examples of such co-regulation.<\/p>\n

In a\u00a0new study<\/a>\u00a0published in\u00a0Genome Research<\/em>\u00a0on October 24, MIT biologists were able to pinpoint specific miRNAs that collaborate with one another to repress mRNA expression in the brain \u2014 adding credence to the notion that miRNAs often collaborate with one another.<\/p>\n

\u201cThe idea that miRNAs may work by co-targeting sets of transcripts together has been around for a while,\u201d says Jennifer Cherone, the study\u2019s lead author. \u201cBut it\u2019s only recently that certain key advances \u2014 like better annotations of where transcripts end and more accurate predictions of miRNA target sites \u2014 have allowed us to uncover these relationships and rigorously test them in the lab.\u201d<\/p>\n

Using powerful computational analyses to compare target sets of different miRNAs, Cherone was able to identify hundreds of distinct miRNAs, which \u2014 despite their sequence differences \u2014 bound many of the same mRNAs. Of all the tissues she examined, the brain appeared to have the most co-targeting. So she narrowed her focus to explore the overlapping functions of just two miRNAs that worked together there: miR-138 and miR-137.<\/p>\n

\u201cThat was a really interesting observation and a functional demonstration of the overlap between these two miRNAs,\u201d she says. \u201cOne miRNA can rescue the loss of a completely different miRNA if they share targets.\u201dIf she deleted miR-138 from her cells, they could no longer differentiate and become neurons. However, when she added miR-138\u2019s co-targeting partner, miR-137, the cells were once again able to differentiate.<\/p>\n

Cherone went on to identify an entire group of miRNAs within the brain, nine in total, that also shared similar targets. She selected several genes targeted by three or more of these miRNAs, and mutated every possible combination of the miRNA sites to determine their individual contributions. She ultimately established that subsets of the miRNAs could repress gene expression between five- and tenfold if they were expressed at the same time and bound close together.<\/p>\n

According to Cherone, \u201cseeing a tenfold repression by miRNAs is unheard of.\u201d Such strong repression\u00a0can have serious phenotypic consequences.\u00a0She attributes\u00a0this finding\u00a0to\u00a0the lab\u2019s advanced computational strategies, which allowed them to systematically and unbiasedly identify\u00a0the miRNAs that work together and their gene targets.<\/p>\n

Why might a single gene be regulated by so many different miRNAs? There are more evolutionary paths to acquire sites for many different miRNAs than paths to acquire sites for the same miRNA. And, the authors explain, this arrangement may allow more precise control of cell type-specific expression.<\/p>\n

Given that their miRNAs of interest primarily worked in the brain, the researchers wondered why this tissue might require so much co-targeting. One idea is that mRNAs in the brain tend to have longer regions where more miRNAs can bind to exert their effects. Another possibility is that mRNA expression in the brain must be especially fine-tuned, because too much or too little expression could have severe ramifications for neuronal function and development. For instance, fragile X-associated tremor\/ataxia syndrome (FXTAS) can result from fairly subtle changes in proteins levels.<\/p>\n

\u201cCo-targeting appears to be widespread in many tissues, not just the brain,\u201d says senior author Christopher Burge, a professor of biology at MIT. \u201cThis means that strategies to modulate the activity of a miRNA in a genetic or therapeutic context will be most effective when they take into account the levels of the other miRNAs that frequently partner with the miRNA of interest.\u201d<\/p>\n

\u201cIt\u2019s time to start thinking of miRNAs as working together in networks, rather than functioning as individual units,\u201d Cherone says. \u201cIf you want to know the function of a given miRNA, you have to understand the group it\u2019s collaborating with, and explore its function within that group.\u201d<\/p>\n

Top image: Graphical illustration of co-targeting by miRNAs. Credit: Jennifer Cherone.<\/h5>\n

Citation:
\n<\/strong>\u201cCotargeting among microRNAs in the brain.\u201d
\nGenome Research,\u00a0<\/i>online October 24, 2019, DOI:\u00a010.1101\/gr.249201.119<\/a>
\nJennifer M. Cherone, Vjola Jorgji, and Christopher B. Burge.<\/p>\n","protected":false},"excerpt":{"rendered":"

A new study from the MIT Department of Biology suggests we may need to re-think how certain RNAs operate to impact development and disease. According to the \u201ccentral dogma\u201d of biology, DNA is converted into messenger RNA (mRNA) before being expressed as a protein. However, not all RNAs are destined to become proteins. MicroRNAs (miRNAs) […]<\/p>\n","protected":false},"author":16,"featured_media":13267,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-13329","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","research-area-genetics","research-area-neurobiology"],"acf":[],"yoast_head":"\nMicroRNAs work together to tune gene expression in the brain - MIT Department of Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"MicroRNAs work together to tune gene expression in the brain\" \/>\n<meta property=\"og:description\" content=\"A new study from the MIT Department of Biology suggests we may need to re-think how certain RNAs operate to impact development and disease. According to the \u201ccentral dogma\u201d of biology, DNA is converted into messenger RNA (mRNA) before being expressed as a protein. However, not all RNAs are destined to become proteins. MicroRNAs (miRNAs) […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/\" \/>\n<meta property=\"og:site_name\" content=\"MIT Department of Biology\" \/>\n<meta property=\"article:published_time\" content=\"2019-11-04T13:58:48+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-10-29T02:33:01+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2019\/10\/Cherone_miRNA_1.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"3627\" \/>\n\t<meta property=\"og:image:height\" content=\"1179\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Raleigh McElvery\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Raleigh McElvery\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/\",\"url\":\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/\",\"name\":\"MicroRNAs work together to tune gene expression in the brain - MIT Department of Biology\",\"isPartOf\":{\"@id\":\"https:\/\/biology.mit.edu\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2019\/10\/Cherone_miRNA_1.jpg\",\"datePublished\":\"2019-11-04T13:58:48+00:00\",\"dateModified\":\"2020-10-29T02:33:01+00:00\",\"author\":{\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66\"},\"breadcrumb\":{\"@id\":\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#primaryimage\",\"url\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2019\/10\/Cherone_miRNA_1.jpg\",\"contentUrl\":\"https:\/\/biology.mit.edu\/wp-content\/uploads\/2019\/10\/Cherone_miRNA_1.jpg\",\"width\":3627,\"height\":1179,\"caption\":\"Illustration of miRNAs\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\/\/biology.mit.edu\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"MicroRNAs work together to tune gene expression in the brain\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/biology.mit.edu\/#website\",\"url\":\"https:\/\/biology.mit.edu\/\",\"name\":\"MIT Department of Biology\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/biology.mit.edu\/?s={search_term_string}\"},\"query-input\":\"required name=search_term_string\"}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66\",\"name\":\"Raleigh McElvery\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/biology.mit.edu\/#\/schema\/person\/image\/\",\"url\":\"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g\",\"contentUrl\":\"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g\",\"caption\":\"Raleigh McElvery\"},\"url\":\"https:\/\/biology.mit.edu\/author\/rmcelvery\/\"}]}<\/script>\n","yoast_head_json":{"title":"MicroRNAs work together to tune gene expression in the brain - MIT Department of Biology","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/","og_locale":"en_US","og_type":"article","og_title":"MicroRNAs work together to tune gene expression in the brain","og_description":"A new study from the MIT Department of Biology suggests we may need to re-think how certain RNAs operate to impact development and disease. According to the \u201ccentral dogma\u201d of biology, DNA is converted into messenger RNA (mRNA) before being expressed as a protein. However, not all RNAs are destined to become proteins. MicroRNAs (miRNAs) […]","og_url":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/","og_site_name":"MIT Department of Biology","article_published_time":"2019-11-04T13:58:48+00:00","article_modified_time":"2020-10-29T02:33:01+00:00","og_image":[{"width":3627,"height":1179,"url":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2019\/10\/Cherone_miRNA_1.jpg","type":"image\/jpeg"}],"author":"Raleigh McElvery","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Raleigh McElvery","Est. reading time":"4 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/","url":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/","name":"MicroRNAs work together to tune gene expression in the brain - MIT Department of Biology","isPartOf":{"@id":"https:\/\/biology.mit.edu\/#website"},"primaryImageOfPage":{"@id":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#primaryimage"},"image":{"@id":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#primaryimage"},"thumbnailUrl":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2019\/10\/Cherone_miRNA_1.jpg","datePublished":"2019-11-04T13:58:48+00:00","dateModified":"2020-10-29T02:33:01+00:00","author":{"@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66"},"breadcrumb":{"@id":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/"]}]},{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#primaryimage","url":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2019\/10\/Cherone_miRNA_1.jpg","contentUrl":"https:\/\/biology.mit.edu\/wp-content\/uploads\/2019\/10\/Cherone_miRNA_1.jpg","width":3627,"height":1179,"caption":"Illustration of miRNAs"},{"@type":"BreadcrumbList","@id":"https:\/\/biology.mit.edu\/micrornas-work-together-to-tune-gene-expression-in-the-brain\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/biology.mit.edu\/"},{"@type":"ListItem","position":2,"name":"MicroRNAs work together to tune gene expression in the brain"}]},{"@type":"WebSite","@id":"https:\/\/biology.mit.edu\/#website","url":"https:\/\/biology.mit.edu\/","name":"MIT Department of Biology","description":"","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/biology.mit.edu\/?s={search_term_string}"},"query-input":"required name=search_term_string"}],"inLanguage":"en-US"},{"@type":"Person","@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/3faf9902afea805a1894ab34b5bddd66","name":"Raleigh McElvery","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/biology.mit.edu\/#\/schema\/person\/image\/","url":"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/2580416cf282b6242f96ed13558deba5?s=96&d=mm&r=g","caption":"Raleigh McElvery"},"url":"https:\/\/biology.mit.edu\/author\/rmcelvery\/"}]}},"_links":{"self":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/13329"}],"collection":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/comments?post=13329"}],"version-history":[{"count":4,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/13329\/revisions"}],"predecessor-version":[{"id":17589,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/posts\/13329\/revisions\/17589"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/media\/13267"}],"wp:attachment":[{"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/media?parent=13329"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/categories?post=13329"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biology.mit.edu\/wp-json\/wp\/v2\/tags?post=13329"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}