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The evolution and expression of the snaR family of small non-coding RNAs.

Parrott AM, Tsai M, Batchu P, Ryan K, Ozer HL, Tian B, Mathews MB - Nucleic Acids Res. (2010)

Bottom Line: We recently identified the snaR family of small non-coding RNAs that associate in vivo with the nuclear factor 90 (NF90/ILF3) protein.The major human species, snaR-A, is an RNA polymerase III transcript with restricted tissue distribution and orthologs in chimpanzee but not rhesus macaque or mouse.We infer that snaR evolved from the left monomer of the primate-specific Alu SINE family via ASR and CAS in conjunction with major primate speciation events, and suggest that snaRs participate in tissue- and species-specific regulation of cell growth and translation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, Newark, New Jersey, USA.

ABSTRACT
We recently identified the snaR family of small non-coding RNAs that associate in vivo with the nuclear factor 90 (NF90/ILF3) protein. The major human species, snaR-A, is an RNA polymerase III transcript with restricted tissue distribution and orthologs in chimpanzee but not rhesus macaque or mouse. We report their expression in human tissues and their evolution in primates. snaR genes are exclusively in African Great Apes and some are unique to humans. Two novel families of snaR-related genetic elements were found 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. ASR and CAS appear to have spread by retrotransposition, whereas most snaR genes have spread by segmental duplication. snaR-A and snaR-G2 are differentially expressed in discrete regions of the human brain and other tissues, notably including testis. snaR-A is up-regulated in transformed and immortalized human cells, and is stably bound to ribosomes in HeLa cells. We infer that snaR evolved from the left monomer of the primate-specific Alu SINE family via ASR and CAS in conjunction with major primate speciation events, and suggest that snaRs participate in tissue- and species-specific regulation of cell growth and translation.

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Dissemination of snaR by segmental duplication. (A) Formation of a hypothetical intermediate by insertion of a fragment of the snaR parent locus (open boxes, snaR in green) into a copy of a region of the DHX34 gene (blue boxes). The insertion point is in long interspersed element (LINE) sequence (hatched), dividing the DHX34 duplicate into ‘5DX’ and ‘3DX’ fragments, separated by 33 bp. The intermediate presumptively served as the source of H- and I-duplicons, which retain 5DX sequence, and of the A/B/C/D-duplicon which retains 3DX sequence. Alu sequences (dark gray boxes) are indicated. snaR transcription directionality within the duplicons is denoted by green arrowhead. (B) Proposed origin of the G-duplicon and origin of CGβ1 and CGβ2 genes (dark blue). Shown is the generation of the G-duplicon from the snaR parental locus and its insertion into a CGβ gene. The substitution of common CGβ gene sequence gave rise to CGβ1 and CGβ2 genes (dark blue). The large curved arrow represents the inverted segmental duplication of the original CGβ1 gene. Bottom: Diagram of the human LH/CGβ gene cluster at chromosome 19q13.33, oriented with respect to centromere (CEN) and telomere (TEL). Arrows indicate direction of transcription.
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Figure 4: Dissemination of snaR by segmental duplication. (A) Formation of a hypothetical intermediate by insertion of a fragment of the snaR parent locus (open boxes, snaR in green) into a copy of a region of the DHX34 gene (blue boxes). The insertion point is in long interspersed element (LINE) sequence (hatched), dividing the DHX34 duplicate into ‘5DX’ and ‘3DX’ fragments, separated by 33 bp. The intermediate presumptively served as the source of H- and I-duplicons, which retain 5DX sequence, and of the A/B/C/D-duplicon which retains 3DX sequence. Alu sequences (dark gray boxes) are indicated. snaR transcription directionality within the duplicons is denoted by green arrowhead. (B) Proposed origin of the G-duplicon and origin of CGβ1 and CGβ2 genes (dark blue). Shown is the generation of the G-duplicon from the snaR parental locus and its insertion into a CGβ gene. The substitution of common CGβ gene sequence gave rise to CGβ1 and CGβ2 genes (dark blue). The large curved arrow represents the inverted segmental duplication of the original CGβ1 gene. Bottom: Diagram of the human LH/CGβ gene cluster at chromosome 19q13.33, oriented with respect to centromere (CEN) and telomere (TEL). Arrows indicate direction of transcription.

Mentions: On the other hand, almost all human and chimpanzee snaRs are surrounded by conserved flanking sequence (8), suggesting that they have disseminated through duplication of a larger encompassing segment or ‘duplicon’. To trace the dispersal of snaR from its presumptive parental locus on chromosome 19 (Figure 3A), we conducted BLAT searches of the well annotated human genome for the ∼1.9 Kb segment containing snaR-F (Supplementary Figure S9 and Supplementary Data S5). This analysis identified partial duplications, each containing a snaR gene with a variable amount of flanking sequence, at the expected locations. From an examination of the flanking sequences in the duplicons, we propose that snaR genes diversified along two independent duplication pathways (Figure 4). The major pathway (Figure 4A), which contains most of the snaR genes, has long duplicons on chromosomes 2 and 3 (including snaR-H and -I) and multiple short duplications in the two large tandem arrays on chromosome 19 (snaR-A, -B, -C and -D). In the second pathway (Figure 4B), two short duplications (including snaR-G1 and -G2) inserted into the LH/CGβ gene cluster gave rise to novel CGβ genes (A.M. Parrott et al., submitted for publication).Figure 4.


The evolution and expression of the snaR family of small non-coding RNAs.

Parrott AM, Tsai M, Batchu P, Ryan K, Ozer HL, Tian B, Mathews MB - Nucleic Acids Res. (2010)

Dissemination of snaR by segmental duplication. (A) Formation of a hypothetical intermediate by insertion of a fragment of the snaR parent locus (open boxes, snaR in green) into a copy of a region of the DHX34 gene (blue boxes). The insertion point is in long interspersed element (LINE) sequence (hatched), dividing the DHX34 duplicate into ‘5DX’ and ‘3DX’ fragments, separated by 33 bp. The intermediate presumptively served as the source of H- and I-duplicons, which retain 5DX sequence, and of the A/B/C/D-duplicon which retains 3DX sequence. Alu sequences (dark gray boxes) are indicated. snaR transcription directionality within the duplicons is denoted by green arrowhead. (B) Proposed origin of the G-duplicon and origin of CGβ1 and CGβ2 genes (dark blue). Shown is the generation of the G-duplicon from the snaR parental locus and its insertion into a CGβ gene. The substitution of common CGβ gene sequence gave rise to CGβ1 and CGβ2 genes (dark blue). The large curved arrow represents the inverted segmental duplication of the original CGβ1 gene. Bottom: Diagram of the human LH/CGβ gene cluster at chromosome 19q13.33, oriented with respect to centromere (CEN) and telomere (TEL). Arrows indicate direction of transcription.
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Figure 4: Dissemination of snaR by segmental duplication. (A) Formation of a hypothetical intermediate by insertion of a fragment of the snaR parent locus (open boxes, snaR in green) into a copy of a region of the DHX34 gene (blue boxes). The insertion point is in long interspersed element (LINE) sequence (hatched), dividing the DHX34 duplicate into ‘5DX’ and ‘3DX’ fragments, separated by 33 bp. The intermediate presumptively served as the source of H- and I-duplicons, which retain 5DX sequence, and of the A/B/C/D-duplicon which retains 3DX sequence. Alu sequences (dark gray boxes) are indicated. snaR transcription directionality within the duplicons is denoted by green arrowhead. (B) Proposed origin of the G-duplicon and origin of CGβ1 and CGβ2 genes (dark blue). Shown is the generation of the G-duplicon from the snaR parental locus and its insertion into a CGβ gene. The substitution of common CGβ gene sequence gave rise to CGβ1 and CGβ2 genes (dark blue). The large curved arrow represents the inverted segmental duplication of the original CGβ1 gene. Bottom: Diagram of the human LH/CGβ gene cluster at chromosome 19q13.33, oriented with respect to centromere (CEN) and telomere (TEL). Arrows indicate direction of transcription.
Mentions: On the other hand, almost all human and chimpanzee snaRs are surrounded by conserved flanking sequence (8), suggesting that they have disseminated through duplication of a larger encompassing segment or ‘duplicon’. To trace the dispersal of snaR from its presumptive parental locus on chromosome 19 (Figure 3A), we conducted BLAT searches of the well annotated human genome for the ∼1.9 Kb segment containing snaR-F (Supplementary Figure S9 and Supplementary Data S5). This analysis identified partial duplications, each containing a snaR gene with a variable amount of flanking sequence, at the expected locations. From an examination of the flanking sequences in the duplicons, we propose that snaR genes diversified along two independent duplication pathways (Figure 4). The major pathway (Figure 4A), which contains most of the snaR genes, has long duplicons on chromosomes 2 and 3 (including snaR-H and -I) and multiple short duplications in the two large tandem arrays on chromosome 19 (snaR-A, -B, -C and -D). In the second pathway (Figure 4B), two short duplications (including snaR-G1 and -G2) inserted into the LH/CGβ gene cluster gave rise to novel CGβ genes (A.M. Parrott et al., submitted for publication).Figure 4.

Bottom Line: We recently identified the snaR family of small non-coding RNAs that associate in vivo with the nuclear factor 90 (NF90/ILF3) protein.The major human species, snaR-A, is an RNA polymerase III transcript with restricted tissue distribution and orthologs in chimpanzee but not rhesus macaque or mouse.We infer that snaR evolved from the left monomer of the primate-specific Alu SINE family via ASR and CAS in conjunction with major primate speciation events, and suggest that snaRs participate in tissue- and species-specific regulation of cell growth and translation.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, New Jersey Medical School, UMDNJ, Newark, New Jersey, USA.

ABSTRACT
We recently identified the snaR family of small non-coding RNAs that associate in vivo with the nuclear factor 90 (NF90/ILF3) protein. The major human species, snaR-A, is an RNA polymerase III transcript with restricted tissue distribution and orthologs in chimpanzee but not rhesus macaque or mouse. We report their expression in human tissues and their evolution in primates. snaR genes are exclusively in African Great Apes and some are unique to humans. Two novel families of snaR-related genetic elements were found 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. ASR and CAS appear to have spread by retrotransposition, whereas most snaR genes have spread by segmental duplication. snaR-A and snaR-G2 are differentially expressed in discrete regions of the human brain and other tissues, notably including testis. snaR-A is up-regulated in transformed and immortalized human cells, and is stably bound to ribosomes in HeLa cells. We infer that snaR evolved from the left monomer of the primate-specific Alu SINE family via ASR and CAS in conjunction with major primate speciation events, and suggest that snaRs participate in tissue- and species-specific regulation of cell growth and translation.

Show MeSH
Related in: MedlinePlus