A screen for nuclear transcripts identified two linked noncoding RNAs associated with SC35 splicing domains. Researchers used Affymetrix expression arrays to identify polyadenylated RNA transcripts enriched in the nucleus. This screen identified three abundant noncoding RNAs: XIST, NEAT1, and NEAT2. XIST is a well-known large noncoding RNA that localizes to the nucleus and is involved in X-chromosome inactivation. NEAT1 and NEAT2 are newly identified noncoding RNAs located on human chromosome 11, less than 70 kb apart. Both are conserved across mammalian species and are enriched in the nucleus. NEAT2 is exceptionally conserved, more so than XIST. Bioinformatic analyses of mouse transcriptome data confirmed that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA fluorescence in situ hybridization (FISH) analyses showed that these noncoding RNAs associate with SC35 nuclear speckles in both human and mouse cells. NEAT1 localizes to the periphery of SC35 domains, while NEAT2 is part of the polyadenylated component of nuclear speckles. These findings suggest that NEAT1 and NEAT2 play a role in mRNA metabolism. The study highlights the importance of noncoding RNAs in nuclear structure and function, particularly in relation to SC35 splicing domains. The identification of these RNAs provides new insights into the molecular mechanisms underlying nuclear organization and mRNA processing.A screen for nuclear transcripts identified two linked noncoding RNAs associated with SC35 splicing domains. Researchers used Affymetrix expression arrays to identify polyadenylated RNA transcripts enriched in the nucleus. This screen identified three abundant noncoding RNAs: XIST, NEAT1, and NEAT2. XIST is a well-known large noncoding RNA that localizes to the nucleus and is involved in X-chromosome inactivation. NEAT1 and NEAT2 are newly identified noncoding RNAs located on human chromosome 11, less than 70 kb apart. Both are conserved across mammalian species and are enriched in the nucleus. NEAT2 is exceptionally conserved, more so than XIST. Bioinformatic analyses of mouse transcriptome data confirmed that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA fluorescence in situ hybridization (FISH) analyses showed that these noncoding RNAs associate with SC35 nuclear speckles in both human and mouse cells. NEAT1 localizes to the periphery of SC35 domains, while NEAT2 is part of the polyadenylated component of nuclear speckles. These findings suggest that NEAT1 and NEAT2 play a role in mRNA metabolism. The study highlights the importance of noncoding RNAs in nuclear structure and function, particularly in relation to SC35 splicing domains. The identification of these RNAs provides new insights into the molecular mechanisms underlying nuclear organization and mRNA processing.