Changing where the polyA tail is added to an mRNA transcript can fine-tune the tissue-specific expression of many genes, reports a Caenorhabditis elegans study published in the June issue of GENETICS. Blazie et al. show alternative polyadenylation (APA) allows transcripts to evade microRNA (miRNA) silencing in some tissues, allowing for tissue-specific expression of those genes. In a thorough study of transcription in eight different tissues, APA stands out as a widespread and previously unappreciated way to regulate genes that are expressed in multiple tissues.

APA occurs after an mRNA is transcribed. Before the transcript can be translated, it must be processed, which includes the addition of a run of adenine bases as the “tail.” Sometimes, post-transcriptional changes to mRNA processing can result in a different protein product or a different expression pattern. Alternative polyadenylation (APA) is a kind of post-transcriptional modification that changes the length of the 3’ untranslated region (UTR) by adding the poly-A tail to an alternative site in the transcript.

The authors obtained the tissue-specific transcriptome of five different C. elegans somatic tissues using a technique called PAT-Seq, which isolates transcripts from a target tissue by expressing a tagged poly-A binding protein in a tissue-specific pattern. PAT-Seq also allows for the precise detection of APA. Combined with previous transcriptome data from three other somatic tissues, this dataset represents the most thorough collection yet of tissue-specific mRNAs in C. elegans, accounting for the tissue-specific expression dynamics of nearly 60% of all annotated protein-coding genes.

Blazie et al. found evidence of APA in all eight somatic tissues they examined—most notably in genes that were expressed in all eight types. Shortening the 3’UTR can have important biological consequences because that is where miRNA target sites are usually found. These short, non-coding RNAs bind to complementary sequences in mRNAs and trigger a pathway that represses the bound transcript. Tissue-specific APA that shortens the 3’UTR and eliminates these miRNA targeting sites releases this regulation and allows translation to occur. Though many of the APA-regulated genes are expressed in multiple tissues, this post-transcriptional modification restricts their biological effect. On average, ubiquitously transcribed genes had longer 3’UTRs enriched with miRNA target sites, and APA eliminates an estimated 37% of these targets.

A closer analysis of the genes rack-1 and tct-1 provides an example—these two genes escape miRNA repression through APA leading to a shorter 3’UTR in muscle tissue. The authors used fluorescently tagged transcripts to show that those with shorter 3’UTRs were not repressed by miRNA in muscle tissue. Knocking down the expression of these genes in muscle tissue also caused embryonic lethality, suggesting that this process is an important regulatory mechanism for development.

Scientists have long known about APA in many organisms, but its significance has not been clear. The development of specific tissue and cell types requires a dynamic genome with multiple layers of gene, transcript, and protein regulation. Not only does this study provide a new resource for future investigation of tissue-specific transcript behavior, it also highlights APA as a regulatory mechanism with widespread consequences.

 

Blazie, S. M., Geissel, H. C., Wilky, H., Joshi, R., Newbern, J., & Mangone, M. (2017). Alternative Polyadenylation Directs Tissue Specific miRNA Targeting in Caenorhabditis elegans Somatic Tissues. GENETICS, 206(2): 757-774. DOI:10.1534/genetics.116.196774

http://www.genetics.org/content/206/2/757

 

Khraiwesh, B. & Salehi-Ashtiani, K. (2017). Commentary: Alternative Poly(A) Tails Meet miRNA Targeting in Caenorhabditis elegans. GENETICS, 206(2): 755-756. DOI:10.1534/genetics.117.202101

http://www.genetics.org/content/206/2/755

, , , ,

Katie is a science writer at GSA. She did her PhD work on the evolutionary consequences of genetic conflict in fruit flies at the University of Georgia.

View all posts by Katie Pieper »

Read more in

  • Ed Grell at his dissecting microscope using ether to anesthetize his flies.

    In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation

    Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…

  • Congratulations to the #Fungal24 Poster Award winners!

    We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…

  • Poster presentation tips for TAGC 2024

    You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…

  • Maximize your TAGC 2024 experience 

    A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…

  • Early Career Leadership Spotlight: Sarah Petrosky

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…

  • TAGC 2024 Early Career Award Winners

    GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024.  Don’t miss the opportunity…

  • Preeminent geneticists recognized with revamped GSA Awards

    In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…

  • Fly Board funds outreach programs to spread the word about Drosophila research

    In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…

  • New members of the GSA Board of Directors: 2024–2026

    We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…

  • A rose-ringed parakeet, one of three parrot species used in the study.

    Parrot plumage study aids breeders and endangered natural populations

    Yellow coloration is maladaptive in the wild but prized by breeders. People have long been fascinated with birds, which exhibit one of the widest ranges of coloration among vertebrates. Parrots, in particular, have captivated humans by their ability to mimic human speech and spectacular plumage. Brightly colored feathers are used primarily to attract mates, intimidate…

  • Early Career Leadership Spotlight: Sarah Gilmour

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah GilmourMultimedia SubcommitteeStowers Institute for Medical Research Research Interest Questions of evolution have always fascinated me. I am extremely fortunate to be starting out my research career in a…