Protein arginine methyltransferase CARM1 attenuates the paraspeckle-mediated nuclear retention of mRNAs containing IR<i>Alu</i>s

<jats:p>In many cells, mRNAs containing inverted repeated <jats:italic>Alu</jats:italic> elements (IR<jats:italic>Alu</jats:italic>s) in their 3′ untranslated regions (UTRs) are inefficiently exported to the cytoplasm. Such nuclear retention correlates with paraspeckle-associated protein complexes containing p54<jats:sup>nrb</jats:sup>. However, nuclear retention of mRNAs containing IR<jats:italic>Alu</jats:italic>s is variable, and how regulation of retention and export is achieved is poorly understood. Here we show one mechanism of such regulation via the arginine methyltransferase CARM1 (coactivator-associated arginine methyltransferase 1). We demonstrate that disruption of CARM1 enhances the nuclear retention of mRNAs containing IR<jats:italic>Alu</jats:italic>s. CARM1 regulates this nuclear retention pathway at two levels: CARM1 methylates the coiled-coil domain of p54<jats:sup>nrb</jats:sup>, resulting in reduced binding of p54<jats:sup>nrb</jats:sup> to mRNAs containing IR<jats:italic>Alu</jats:italic>s, and also acts as a transcription regulator to suppress <jats:italic>NEAT1</jats:italic> transcription, leading to reduced paraspeckle formation. These actions of CARM1 work together synergistically to regulate the export of transcripts containing IR<jats:italic>Alu</jats:italic>s from paraspeckles under certain cellular stresses, such as poly(I:C) treatment. This work demonstrates how a post-translational modification of an RNA-binding protein affects protein–RNA interaction and also uncovers a mechanism of transcriptional regulation of the long noncoding RNA <jats:italic>NEAT1</jats:italic>.</jats:p>