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Identification of novel homologous microRNA genes in the rhesus macaque genome.

Yue J, Sheng Y, Orwig KE - BMC Genomics (2008)

Bottom Line: We compared the total 454 miRNAs identified so far in rhesus to human homologs, 173 miRNA genes showed 100% homology in precursor sequences between rhesus and human; The remaining 281 show more than 90%, less than 100% homology in precursor sequences.Identification of miRNA genes in rhesus will provide the resources for analysis of expression profiles in various tissues by creating a rhesus miRNA array, which is currently not available for this species.Investigation of rhesus miRNAs will also expand our understanding of their biological function through miRNA knockout, knockdown or overexpression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. jyue@pdc.magee.edu

ABSTRACT

Background: MicroRNAs (miRNAs) are about 22 nucleotide (nt) endogenous small RNAs that negatively regulate gene expression. They are a recently described class of regulatory molecules that has biological implications for tumorigenesis, development, metabolism and viral diseases. To date, 533 miRNAs have been identified in human. However, only 71 miRNAs have been reported in rhesus macaque. The rhesus is widely used in medical research because of its genetic and physiological similarity to human. The rhesus shares approximately 93% similarity with human in genome sequences and miRNA genes are evolutionarily conserved. Therefore, we searched the rhesus genome for sequences similar to human miRNA precursor sequences to identify putative rhesus miRNA genes.

Results: In addition to 71 miRNAs previously reported, we identified 383 novel miRNA genes in the rhesus genome. We compared the total 454 miRNAs identified so far in rhesus to human homologs, 173 miRNA genes showed 100% homology in precursor sequences between rhesus and human; The remaining 281 show more than 90%, less than 100% homology in precursor sequences. Some miRNAs in the rhesus genome are present as clusters similar to human, such as miR-371/373, miR-367/302b, miR-17/92, or have multiple copies distributed in the same or different chromosomes. RT-PCR analysis of expression of eight rhesus miRNA genes in rhesus tissues demonstrated tissue-specific regulation of expression.

Conclusion: Identification of miRNA genes in rhesus will provide the resources for analysis of expression profiles in various tissues by creating a rhesus miRNA array, which is currently not available for this species. Investigation of rhesus miRNAs will also expand our understanding of their biological function through miRNA knockout, knockdown or overexpression.

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MiRNA clusters in the human genome aligned with homologous regions of the rhesus, mouse and rat genomes. (A) Human cluster miR-371/373 is located on chr19: 58,982,741–58,983,839 (1099 bp, [27]), Rhesus has the similar cluster also located on chr19 in rhesus. This cluster is not well conserved in mice and rats. (B) Human cluster miR-367/302b is on chr4: 113,926,634–113,927,317 [27] and hosted in antisense orientation in a 684 bp region, in rhesus and mouse. There is no similar cluster in rat genome. (C) Human miR-17/92 cluster is located on chr13: 90,800,860–90,801,646(787 bp, [27]) and is highly conserved among in the rhesus, mouse, and rat genomes.
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Figure 1: MiRNA clusters in the human genome aligned with homologous regions of the rhesus, mouse and rat genomes. (A) Human cluster miR-371/373 is located on chr19: 58,982,741–58,983,839 (1099 bp, [27]), Rhesus has the similar cluster also located on chr19 in rhesus. This cluster is not well conserved in mice and rats. (B) Human cluster miR-367/302b is on chr4: 113,926,634–113,927,317 [27] and hosted in antisense orientation in a 684 bp region, in rhesus and mouse. There is no similar cluster in rat genome. (C) Human miR-17/92 cluster is located on chr13: 90,800,860–90,801,646(787 bp, [27]) and is highly conserved among in the rhesus, mouse, and rat genomes.

Mentions: MiRNA genes tend to be present as clusters in the genome [34,35]. Clusters were previously defined by Weber [36] as miRNA genes present in the same orientation and not separated by a transcriptional unit. Altuvia and colleagues [37] demonstrated that 42% of known human miRNA genes are arranged in clusters in the genome using a 3 kb threshold between two miRNA genes or 48% if the threshold is 10 kb. We found that at least some rhesus miRNAs are also arranged in clusters in the rhesus genome. Here we listed three human miRNA clusters (Figure 1) that have been associated with specific functions in previous studies. These miRNA clusters are located in regions of the genome that display substantial evolutionary conservation among 17 vertebrate species listed in the UCSC Genome Bioinformatics database: [27-29,38]. Sequence conservation in these regions of the human genome with rhesus, mouse and rat are indicated (Figure 1). Cluster miR-371/373 is located on chromosome 19 in human and rhesus, is expressed in human ES cells [18] and functions as an oncogene in human testicular carcinomas [21]. Rhesus miR-372 and miR-373 have 100% similarity in mature miRNA sequences with the human orthologs. Rhesus miR-371 has one nucleotide mismatch with the human sequence and rhesus miR-373* has three nucleotide differences (Table 2, Figure 1A). The mature sequences for miR-373 and miR-373* are encoded from the same pre-miRNA on complementary strands of the hairpin stem (see additional file 1).


Identification of novel homologous microRNA genes in the rhesus macaque genome.

Yue J, Sheng Y, Orwig KE - BMC Genomics (2008)

MiRNA clusters in the human genome aligned with homologous regions of the rhesus, mouse and rat genomes. (A) Human cluster miR-371/373 is located on chr19: 58,982,741–58,983,839 (1099 bp, [27]), Rhesus has the similar cluster also located on chr19 in rhesus. This cluster is not well conserved in mice and rats. (B) Human cluster miR-367/302b is on chr4: 113,926,634–113,927,317 [27] and hosted in antisense orientation in a 684 bp region, in rhesus and mouse. There is no similar cluster in rat genome. (C) Human miR-17/92 cluster is located on chr13: 90,800,860–90,801,646(787 bp, [27]) and is highly conserved among in the rhesus, mouse, and rat genomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2254598&req=5

Figure 1: MiRNA clusters in the human genome aligned with homologous regions of the rhesus, mouse and rat genomes. (A) Human cluster miR-371/373 is located on chr19: 58,982,741–58,983,839 (1099 bp, [27]), Rhesus has the similar cluster also located on chr19 in rhesus. This cluster is not well conserved in mice and rats. (B) Human cluster miR-367/302b is on chr4: 113,926,634–113,927,317 [27] and hosted in antisense orientation in a 684 bp region, in rhesus and mouse. There is no similar cluster in rat genome. (C) Human miR-17/92 cluster is located on chr13: 90,800,860–90,801,646(787 bp, [27]) and is highly conserved among in the rhesus, mouse, and rat genomes.
Mentions: MiRNA genes tend to be present as clusters in the genome [34,35]. Clusters were previously defined by Weber [36] as miRNA genes present in the same orientation and not separated by a transcriptional unit. Altuvia and colleagues [37] demonstrated that 42% of known human miRNA genes are arranged in clusters in the genome using a 3 kb threshold between two miRNA genes or 48% if the threshold is 10 kb. We found that at least some rhesus miRNAs are also arranged in clusters in the rhesus genome. Here we listed three human miRNA clusters (Figure 1) that have been associated with specific functions in previous studies. These miRNA clusters are located in regions of the genome that display substantial evolutionary conservation among 17 vertebrate species listed in the UCSC Genome Bioinformatics database: [27-29,38]. Sequence conservation in these regions of the human genome with rhesus, mouse and rat are indicated (Figure 1). Cluster miR-371/373 is located on chromosome 19 in human and rhesus, is expressed in human ES cells [18] and functions as an oncogene in human testicular carcinomas [21]. Rhesus miR-372 and miR-373 have 100% similarity in mature miRNA sequences with the human orthologs. Rhesus miR-371 has one nucleotide mismatch with the human sequence and rhesus miR-373* has three nucleotide differences (Table 2, Figure 1A). The mature sequences for miR-373 and miR-373* are encoded from the same pre-miRNA on complementary strands of the hairpin stem (see additional file 1).

Bottom Line: We compared the total 454 miRNAs identified so far in rhesus to human homologs, 173 miRNA genes showed 100% homology in precursor sequences between rhesus and human; The remaining 281 show more than 90%, less than 100% homology in precursor sequences.Identification of miRNA genes in rhesus will provide the resources for analysis of expression profiles in various tissues by creating a rhesus miRNA array, which is currently not available for this species.Investigation of rhesus miRNAs will also expand our understanding of their biological function through miRNA knockout, knockdown or overexpression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. jyue@pdc.magee.edu

ABSTRACT

Background: MicroRNAs (miRNAs) are about 22 nucleotide (nt) endogenous small RNAs that negatively regulate gene expression. They are a recently described class of regulatory molecules that has biological implications for tumorigenesis, development, metabolism and viral diseases. To date, 533 miRNAs have been identified in human. However, only 71 miRNAs have been reported in rhesus macaque. The rhesus is widely used in medical research because of its genetic and physiological similarity to human. The rhesus shares approximately 93% similarity with human in genome sequences and miRNA genes are evolutionarily conserved. Therefore, we searched the rhesus genome for sequences similar to human miRNA precursor sequences to identify putative rhesus miRNA genes.

Results: In addition to 71 miRNAs previously reported, we identified 383 novel miRNA genes in the rhesus genome. We compared the total 454 miRNAs identified so far in rhesus to human homologs, 173 miRNA genes showed 100% homology in precursor sequences between rhesus and human; The remaining 281 show more than 90%, less than 100% homology in precursor sequences. Some miRNAs in the rhesus genome are present as clusters similar to human, such as miR-371/373, miR-367/302b, miR-17/92, or have multiple copies distributed in the same or different chromosomes. RT-PCR analysis of expression of eight rhesus miRNA genes in rhesus tissues demonstrated tissue-specific regulation of expression.

Conclusion: Identification of miRNA genes in rhesus will provide the resources for analysis of expression profiles in various tissues by creating a rhesus miRNA array, which is currently not available for this species. Investigation of rhesus miRNAs will also expand our understanding of their biological function through miRNA knockout, knockdown or overexpression.

Show MeSH
Related in: MedlinePlus