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  • Behm, Mikaela,1986-Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut (author)

Synaptic expression and regulation of miRNA editing in the brain

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  • LIBRIS-ID:oai:DiVA.org:su-142315
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-142315URI

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  • Language:English
  • Summary in:English

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  • Subject category:vet swepub-contenttype
  • Subject category:ovr swepub-publicationtype

Notes

  • In the brain, sophisticated networks of RNA regulatory events tightly control gene expression in order to achieve proper brain function. We and others have previously shown that several miRNAs, encoded within the miR-379-410 cluster, are subjected to A-to-I RNA editing. In the present study we conclude these edited miRNAs to be transcribed as a single long consecutive transcript, however the maturation into functional forms of miRNAs is regulated individually. In seven of the miRNAs, subjected to editing, we analyze how editing relates to miRNA maturation. Of particular interest has been maturation of miR-381-3p and miR-376b-3p, both important for neuronal plasticity, dendrite outgrowth and neuronal homeostasis. Most of the edited miRNAs from the cluster, are highly edited in their unprocessed primary transcript, including miR-381-3p and miR-376b-3p. However, editing in miR-381-3p is almost entirely absent in the mature form, while editing is increased in the mature form of miR-376b-3p compared to the primary transcript. We propose that ADAR1 positively influences the maturation of pri-miR-381 in an editing independent manner. In pri-miR-376b we hypothesize that ADAR1 and ADAR2 competes for editing, and while ADAR2 inhibits miRNA maturation, ADAR1 editing is frequently present in the mature miR-376b-3p. We further show that miR-381-3p and miR-376b-3p regulate the dendritically expressed Pumilio 2 (Pum2) protein. By next generation RNA sequencing (NGS RNA-seq) on purified synaptoneurosomes, we show that miR-381-3p is highly expressed at the synapse, suggesting its functional role in locally regulating Pum2. Furthermore, we identify a set of highly expressed miRNAs at the synapse, which may act locally to target synaptic mRNAs.

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  • Fritzell, KajsaStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)kafr3086 (author)
  • Pessa, Heli (author)
  • Mackowiak, SebastianStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)smack (author)
  • Ekdahl, Ylva (author)
  • Kang, WenjingStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)wkang (author)
  • Biryukova, InnaStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)einna (author)
  • von Euler, AnneStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)avone (author)
  • Visa, NeusStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)neus (author)
  • Friedländer, MarcStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)mfrie (author)
  • Öhman, MarieStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)marohm (author)
  • Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)

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