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snaR: small NF90-associated RNAs
~117nt. RNA polymerase III transcripts. Highly structured. snaR genes shares sequence identity with Alu RNA and two potential piRNAs. Cloned snaR sequences have a run of adenines in the 3' end followed by a run of thymidines (which presumably constitute the PolIII termination site) (Parrott (2007)). snaR-A and snaR-B were originally identified associated to the Nuclear factor 90 (NF90) (a double-stranded RNA-binding protein implicated in multiple cellular functions) by in vivo cross-linking followed by immunoprecipitation.RNA species immunoprecipitated with NF90 were ~80®C120 nt long (Parrott (2007)). Several related RNAs of ~104 nt were originally cloned and identified, with snaR-A being the major component, and snaR-B representing the minor subset. snaR-A and snaR-B are ~90% identical in sequence. Human genomic sequences corresponding to snaR-A and snaR-B have occasional mismatches (suggested to be possibly due to C-to-U editing of the RNA). snaR genes occur in multiple copies (accumulated by segmental duplication) arranged in two inverted regions of tandem repeats on human chromosome 19. Additional snaR gene copies are present, with two of them adjacent to genes encoding the beta chain of chorionic gonadotropin:. In total, 28 snaR genes have been identified in the human genome, including 14 genes for snaR-A and 2 genes for snaR-B. snaR genes identified by sequence analysis include 5 snaR-C genes and additional genes (snaR-D, -E, -F, -G1, -G2, -H, -I, -12 and -21) (Parrott (2007)). snaR-D to -G include 5 unique genes on chromosome 19 as well as single copies (snaR-2 and -3) on chromosomes 2 and 3. snaR-G1 and -G2 are located in a gene-rich 2.1 Mb genomic fragment between the two clusters, lying within the promoter region of two genes encoding the beta polypeptide of chorionic gonadotropin (CG-beta) (Parrott (2007)).
Functions of snaR transcripts have not been identified yet. snaR transcripts interact with NF90's double-stranded RNA-binding motifs (dsRBMs) (Parrott (2007)), and snaR-A is also found stably bound to ribosomes in HeLa cells (Parrott et al. 2010). Suggested to be involved in tissue- and species-specific regulation of cell growth and translation (Parrott (2007), Parrott (2009), Parrott (2010)).
Predominantly cytoplasmic, unstable (half-life of ~15 min in HeLa cells), expressed in diverse cell lines and human tissues. The different snaR genes have different expression levels and profiles, and, among more than 20 adult human tissues analysed, snaR transcripts are found particularly abundant in testis, with low levels detected in brain, placenta and some other organs. (Parrott (2007), Parrott (2010)). Highly abundant in some cells, with snaR-A estimated in ~70,000 copies in a HEK293T cell (Parrott (2007)). snaR-A and snaR-G2 are differentially expressed in discrete regions of the human brain and other tissues, such as testis (Parrott (2010)). snaR-A was expression n testis was ~100-fold higher than in term placenta, lung and adipose tissue, and in brain its levels were ~10% of the testis level in three of four segments of pituitary gland, with substantial expression also observed in other brain regions (such as hypothalamus, globus pallidus and thalamus) (Parrott (2010)). snaR-G2 levels in adult brain were ~55% of that in testis (highest in caudate/accumbens/putamen and globus pallidus), and several tissues displayed 5®C15% of testis levels. Fetal brain contained much less snaR-G2 than adult brain (~3% of testis level), suggestive of developmental regulation. (Parrott (2010)). snaR-A is up-regulated in transformed and immortalized human cells (Parrott et al. 2010).
snaR genes are present exclusively in African Great Apes and some are unique to humans. Human snaR-A has orthologs in chimpanzee but not rhesus macaque or mouse. Chimpanzee has fewer snaR genes than humans (10 instead of 28). snaRs appear to have undergone accelerated evolution (snaR genes display a lower degree of homology within the gene than in their flanking sequence) and differential expansion in the great apes. (Parrott (2007), Parrott et al. 2010). There are ~17 nt changes between human snaR-A (121nt) and snaR-C (119nt) species (~14% difference), compared to an average substitution rate of ~3.7?nt per 120nt (~3% difference) outside of the snaR locus (Parrott (2010)). The single snaR gene on chimpanzee chromosome 2a is 94% identical with its ortholog on human chromosome 2, and two genes on chimpanzee chromosome 19 are orthologous with snaR-G1 (a unique gene on human chromosome 19). The position of these snaR genes relative to the primate-specific CG-beta genes is conserved. (Parrott (2007)).
- Two families of snaR-related genetic elements were identified in primates: CAS (catarrhine ancestor of snaR), limited to Old World Monkeys and apes; and ASR (Alu/snaR-related), present in all monkeys and apes. These two classes appear to have spread by retrotransposition. It has been proposed that snaR genes evolved through a series of internal deletions and expansions from the left monomer of the primate-specific Alu SINE family via ASR and CAS (Parrott (2010)). *Short RNAs of ~26®C34 nt can be detected after long exposure of Northern blots with snaR probes (Parrott (2007)). *Other RNAs are also found associated with NF90, including viral RNAs, such as the VAI and VAII noncoding RNAs from human adenoviruses (Liao (1998)).
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Labs working on this lncRNA
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