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

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. However, we didn’t find IRAlus in 3’UTR of the paraspeckle target RNAs, we previously identified in a pituitary cell line. Since 3’UTR of mRNA are known to contain sequence recognition for nuclear localization, we search for other potential RNA recruitment elements in the 3’UTR of a candidate paraspeckle target gene, namely calreticulin mRNA. We found a 15 nucleotides 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 3’UTR mRNAs. In addition, since this sequence binds the paraspeckle protein component HNRNPK, it is proposed that HNRNPK constitute a bridging protein between paraspeckles and target mRNAs.