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Pré-Publication, Document De Travail Année : 2020

A Sequence determinant in 3’UTR of mRNAs for Nuclear Retention by Paraspeckles

Résumé

Paraspeckles are nuclear membraneless structures composed of a long non-coding RNA, Nuclear-Enriched-Abundant-Transcript-1 and RNA binding proteins, which associate numerous mRNAs. It is therefore believed that their cellular function is to sequester in the nucleus their associated proteins and/or target mRNAs. However, little is known about the molecular determinant in mRNA targets that allow their association to paraspeckles except that inverted repeats of Alu sequences (IRAlu) present in 3’UTR of mRNAs may allow this association. While in a previous study we established the list of paraspeckle target RNAs in a rat pituitary cell line, we didn’t find however, inverted repeated SINEs, the rat equivalent of primate IRAlus in 3’UTR of these RNAs. By developing a candidate gene strategy, we selected a paraspeckle target gene, namely calreticulin mRNA, and we searched for other potential RNA recruitment elements in its 3’UTR, since 3’UTRs usually contain the sequence recognition for nuclear localization. We found a 15-nucleotide sequence, present as a tandem repeat in 3’UTR of this mRNA, which is involved in the nuclear retention by paraspeckles. While being not overrepresented in the 3’UTR of the paraspeckle target RNAs, this recruitment element was present in near 30% of all 3’UTR mRNAs. In addition, since an oligonucleotide containing this sequence binds the paraspeckle protein component HNRNPK, it is proposed that HNRNPK may constitute a bridging protein between paraspeckles and target mRNAs.
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Dates et versions

hal-03007531 , version 1 (08-12-2020)

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Audrey Jacq, Denis Becquet, Bénédicte Boyer, Séverine Guillen, Maria-Montserrat Bello-Goutierrez, et al.. A Sequence determinant in 3’UTR of mRNAs for Nuclear Retention by Paraspeckles. 2020. ⟨hal-03007531⟩
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