Paraspeckles – where long noncoding RNA meets phase separation

Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles – protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA–protein and protein–protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here researchers from the University of Western Australia discuss the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings.

Paraspeckles Regulate Gene Expression by Sequestration and Enhancing
the Efficiency of Paraspeckle Protein Function

lncRNA

The steady state is depicted in the center, with paraspeckle proteins and targeted structured RNAs found both inside paraspeckles and elsewhere in the nucleus, including regulating gene transcription at promoters. When the paraspeckle proteins are organized inside paraspeckles, there is evidence for enhanced processing of pri-miRNA transcripts. The right panel depicts what happens when cells become stressed, or NEAT1_2 is increased. In this instance, paraspeckles elongate, increasing the sequestration of paraspeckle proteins, with the pool of nucleoplasmic paraspeckle protein diminishing, resulting in a change in transcription of target genes. The left panel shows what happens when NEAT1_2 levels decrease, either in a particular stage of the circadian cycle, in cells that do not express NEAT1_2, or when NEAT1_2 is artificially reduced. In this instance, paraspeckle proteins and regulated RNAs are free to bind to target gene promoters, or, in the case of regulated RNAs, to be exported from the nucleus and used as templates for translation. The efficiency of pri-miRNA processing by paraspeckle proteins is diminished. NEAT1, nuclear paraspeckle assembly transcript 1.

Fox AH, Nakagawa S, Hirose T, Bond CS. (2017) Paraspeckles: Where Long Noncoding RNA Meets Phase Separation. Trends in Biochem Sci [Epub ahead of print]. [abstract]

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