Proteins of the Drosophila behavior/human splicing (DBHS) family include 
mammalian SFPQ (PSF), NONO (p54nrb), PSPC1, and invertebrate NONA and Hrp65. 
DBHS proteins are predominately nuclear, and are involved in transcriptional and 
posttranscriptional gene regulatory functions as well as DNA repair. DBHS 
proteins influence a wide gamut of biological processes, including the 
regulation of circadian rhythm, carcinogenesis, and progression of cancer. 
Additionally, mammalian DBHS proteins associate with the architectural long 
noncoding RNA NEAT1 (Menε/β) to form paraspeckles, subnuclear bodies that alter 
gene expression via the nuclear retention of RNA. Here we describe the crystal 
structure of the heterodimer of the multidomain conserved region of the DBHS 
proteins, PSPC1 and NONO. These proteins form an extensively intertwined dimer, 
consistent with the observation that the different DBHS proteins are typically 
copurified from mammalian cells, and suggesting that they act as obligate 
heterodimers. The PSPC1/NONO heterodimer has a right-handed antiparallel 
coiled-coil that positions two of four RNA recognition motif domains in an 
unprecedented arrangement on either side of a 20-Å channel. This configuration 
is supported by a protein:protein interaction involving the NONA/paraspeckle 
domain, which is characteristic of the DBHS family. By examining various mutants 
and truncations in cell culture, we find that DBHS proteins require an 
additional antiparallel coiled-coil emanating from either end of the dimer for 
paraspeckle subnuclear body formation. These results suggest that paraspeckles 
may potentially form through self-association of DBHS dimers into higher-order 
structures.