Paraspeckle nuclear bodies--useful uselessness?

Abstract

The nucleus of higher eukaryotes, such as humans and mice, is compartmentalized into multiple nuclear bodies, an organization that allows for the regulation of complex gene expression pathways that are characteristic of these organisms. Paraspeckles are recently discovered, mammalian-specific nuclear bodies built on a long, non-protein-coding RNA, NEAT1 (nuclear-enriched abundant transcript 1), which assembles various protein components including RNA-binding proteins of the DBHS (Drosophila behavior and human splicing) family. Paraspeckles have been proposed to control several biological processes, such as stress responses and cellular differentiation, but their function at the whole animal level remains unclear. In this review, we summarize a series of studies on paraspeckles that have been carried out in the decade since their discovery and discuss their physiological function and molecular mechanism.

Fig. 1

The nuclear body paraspeckle and its provisional ultrastructure model. a Expression of NEAT1 (green) and PSF (magenta) in MEFs. Each nucleus typically contains 5–10 paraspeckles. b Provisional ultrastructure model of paraspeckles. NEAT1 transcripts are radially arranged perpendicular to the longer axis of paraspeckles with the 5′ and 3′ ends of the transcripts facing outward. Note that the precise stoichiometry of each paraspeckle components is not known

Fig. 2

Co-transcriptional assembly of paraspeckle components at the NEAT1 transcription site. Paraspeckle components bind to newly synthesized NEAT1 transcripts at the transcription site to form paraspeckles. The transcript of NEAT1_2, the longer isoform of NEAT1, may function by either providing more entry sites for the paraspeckle components (a) or tethering NEAT1_1 at the transcription site for a longer period, allowing sufficient time for the nuclear bodies to form (b)

Fig. 3

Expression of NEAT1_1 and NEAT1_2 in vivo. Both NEAT1 isoforms are ubiquitously expressed in cultured cell lines, but NEAT1_1 is expressed in particular cell types, and NEAT1_2 expression is further restricted to a small number of cells in particular regions. a Expression of NEAT1_1/2 in the intestine, colon, and spleen. In the gut, NEAT1_2 is expressed in a region where natural cell loss occurs. In the spleen, only megakaryocytes express NEAT1_2. b Distribution of ESTs in the public genome database, UCSC genome browser (http://genome.ucsc.edu/). Much smaller numbers of ESTs are mapped to NEAT1_2 -specific regions

Fig. 4

Possible functional mode of paraspeckles. Paraspeckles may function as “positive” nuclear bodies by mediating certain molecular process within the nuclear bodies. Alternatively, paraspeckles may function as “negative” nuclear bodies by sequestering active protein factors that function in other regions of the nucleus