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Genome-wide annotation and analysis of zebra finch microRNA repertoire reveal sex-biased expression.

Luo GZ, Hafner M, Shi Z, Brown M, Feng GH, Tuschl T, Wang XJ, Li X - BMC Genomics (2012)

Bottom Line: Among them, miR-2954, an avian specific miRNA, is expressed at significantly higher levels in males than in females in all tissues examined.Our genome-wide systematic analysis of mature sequences, genomic locations, evolutionary sequence conservation, and tissue expression profiles of the zebra finch miRNA repertoire provides a valuable resource to the research community.Our analysis also reveals a miRNA-mediated mechanism that potentially regulates sex-biased gene expression in avian species.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Kay Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

ABSTRACT

Background: MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally in a wide range of biological processes. The zebra finch (Taeniopygia guttata), an oscine songbird with characteristic learned vocal behavior, provides biologists a unique model system for studying vocal behavior, sexually dimorphic brain development and functions, and comparative genomics.

Results: We deep sequenced small RNA libraries made from the brain, heart, liver, and muscle tissues of adult male and female zebra finches. By mapping the sequence reads to the zebra finch genome and to known miRNAs in miRBase, we annotated a total of 193 miRNAs. Among them, 29 (15%) are avian specific, including three novel zebra finch specific miRNAs. Many of the miRNAs exhibit sequence heterogeneity including length variations, untemplated terminal nucleotide additions, and internal substitution events occurring at the uridine nucleotide within a GGU motif. We also identified seven Z chromosome-encoded miRNAs. Among them, miR-2954, an avian specific miRNA, is expressed at significantly higher levels in males than in females in all tissues examined. Target prediction analysis reveals that miR-2954, but not other Z-linked miRNAs, preferentially targets Z chromosome-encoded genes, including several genes known to be expressed in a sexually dimorphic manner in the zebra finch brain.

Conclusions: Our genome-wide systematic analysis of mature sequences, genomic locations, evolutionary sequence conservation, and tissue expression profiles of the zebra finch miRNA repertoire provides a valuable resource to the research community. Our analysis also reveals a miRNA-mediated mechanism that potentially regulates sex-biased gene expression in avian species.

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miRNA sequence variants. (A) Distribution of sequence variation types among all miRNA reads. (B) Sequence variants in miR-124. The nucleotides differing from the template genome are highlighted in red. Blue bars to the right indicate frequencies of these variants. (C) Motifs identified among internal substitution sites. The overall height of a stack indicates sequence conservation at that position: the higher the stack, the more the position is conserved. The heights of nucleotides within a stack indicate the relative frequency for each nucleotide at that position. We analyzed 6-nucleotide sequences containing an internal substitution site having a substitution rate > 5%, and found that a GGU motif was preferentially present among all sequences. The numbers (1–6) below the X axis indicate nucleotide positions in the motifs.
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Figure 4: miRNA sequence variants. (A) Distribution of sequence variation types among all miRNA reads. (B) Sequence variants in miR-124. The nucleotides differing from the template genome are highlighted in red. Blue bars to the right indicate frequencies of these variants. (C) Motifs identified among internal substitution sites. The overall height of a stack indicates sequence conservation at that position: the higher the stack, the more the position is conserved. The heights of nucleotides within a stack indicate the relative frequency for each nucleotide at that position. We analyzed 6-nucleotide sequences containing an internal substitution site having a substitution rate > 5%, and found that a GGU motif was preferentially present among all sequences. The numbers (1–6) below the X axis indicate nucleotide positions in the motifs.

Mentions: Taking advantage of the large sequence dataset, we analyzed miRNA sequence variations. We classified miRNA isoforms into three major groups: length variations, untemplated terminal nucleotide additions, and internal substitutions (Figure4A). The length variants accounted for 25% of the total miRNA reads, a majority of which (> 80%) were 3' variants (Figure4A). This is in good agreement with observations in other species, further supporting the notion that precision at cleavage events at the 5'-termini is necessary to protect the seed sequence at positions 2–8 of the mature miRNA[12,44,45]. Nonetheless, the read numbers of 5' offset isoforms of several miRNAs were relatively high. For example, miR-124, a brain enriched miRNA, had several 5' offset isoforms, with the combined reads accounting for 15% of all reads (Figure4B). Another prominent example was miR-133a, which had two main 5'-isoforms, miR-133a1 and miR-133a2, of which the 5' terminus of miR-133a2 was shifted 1 nucleotide in the 3' direction. These two isoforms were each represented by 77,642 and 98,840 reads, accounting for 32% and 41% of the total reads. Interestingly, similar patterns of 5' heterogeneity are also observed in mouse miR-124 and miR-133a[12,46], indicating that the alternative processing mechanisms giving raise to these isoforms might be evolutionarily conserved.


Genome-wide annotation and analysis of zebra finch microRNA repertoire reveal sex-biased expression.

Luo GZ, Hafner M, Shi Z, Brown M, Feng GH, Tuschl T, Wang XJ, Li X - BMC Genomics (2012)

miRNA sequence variants. (A) Distribution of sequence variation types among all miRNA reads. (B) Sequence variants in miR-124. The nucleotides differing from the template genome are highlighted in red. Blue bars to the right indicate frequencies of these variants. (C) Motifs identified among internal substitution sites. The overall height of a stack indicates sequence conservation at that position: the higher the stack, the more the position is conserved. The heights of nucleotides within a stack indicate the relative frequency for each nucleotide at that position. We analyzed 6-nucleotide sequences containing an internal substitution site having a substitution rate > 5%, and found that a GGU motif was preferentially present among all sequences. The numbers (1–6) below the X axis indicate nucleotide positions in the motifs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585881&req=5

Figure 4: miRNA sequence variants. (A) Distribution of sequence variation types among all miRNA reads. (B) Sequence variants in miR-124. The nucleotides differing from the template genome are highlighted in red. Blue bars to the right indicate frequencies of these variants. (C) Motifs identified among internal substitution sites. The overall height of a stack indicates sequence conservation at that position: the higher the stack, the more the position is conserved. The heights of nucleotides within a stack indicate the relative frequency for each nucleotide at that position. We analyzed 6-nucleotide sequences containing an internal substitution site having a substitution rate > 5%, and found that a GGU motif was preferentially present among all sequences. The numbers (1–6) below the X axis indicate nucleotide positions in the motifs.
Mentions: Taking advantage of the large sequence dataset, we analyzed miRNA sequence variations. We classified miRNA isoforms into three major groups: length variations, untemplated terminal nucleotide additions, and internal substitutions (Figure4A). The length variants accounted for 25% of the total miRNA reads, a majority of which (> 80%) were 3' variants (Figure4A). This is in good agreement with observations in other species, further supporting the notion that precision at cleavage events at the 5'-termini is necessary to protect the seed sequence at positions 2–8 of the mature miRNA[12,44,45]. Nonetheless, the read numbers of 5' offset isoforms of several miRNAs were relatively high. For example, miR-124, a brain enriched miRNA, had several 5' offset isoforms, with the combined reads accounting for 15% of all reads (Figure4B). Another prominent example was miR-133a, which had two main 5'-isoforms, miR-133a1 and miR-133a2, of which the 5' terminus of miR-133a2 was shifted 1 nucleotide in the 3' direction. These two isoforms were each represented by 77,642 and 98,840 reads, accounting for 32% and 41% of the total reads. Interestingly, similar patterns of 5' heterogeneity are also observed in mouse miR-124 and miR-133a[12,46], indicating that the alternative processing mechanisms giving raise to these isoforms might be evolutionarily conserved.

Bottom Line: Among them, miR-2954, an avian specific miRNA, is expressed at significantly higher levels in males than in females in all tissues examined.Our genome-wide systematic analysis of mature sequences, genomic locations, evolutionary sequence conservation, and tissue expression profiles of the zebra finch miRNA repertoire provides a valuable resource to the research community.Our analysis also reveals a miRNA-mediated mechanism that potentially regulates sex-biased gene expression in avian species.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Kay Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

ABSTRACT

Background: MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally in a wide range of biological processes. The zebra finch (Taeniopygia guttata), an oscine songbird with characteristic learned vocal behavior, provides biologists a unique model system for studying vocal behavior, sexually dimorphic brain development and functions, and comparative genomics.

Results: We deep sequenced small RNA libraries made from the brain, heart, liver, and muscle tissues of adult male and female zebra finches. By mapping the sequence reads to the zebra finch genome and to known miRNAs in miRBase, we annotated a total of 193 miRNAs. Among them, 29 (15%) are avian specific, including three novel zebra finch specific miRNAs. Many of the miRNAs exhibit sequence heterogeneity including length variations, untemplated terminal nucleotide additions, and internal substitution events occurring at the uridine nucleotide within a GGU motif. We also identified seven Z chromosome-encoded miRNAs. Among them, miR-2954, an avian specific miRNA, is expressed at significantly higher levels in males than in females in all tissues examined. Target prediction analysis reveals that miR-2954, but not other Z-linked miRNAs, preferentially targets Z chromosome-encoded genes, including several genes known to be expressed in a sexually dimorphic manner in the zebra finch brain.

Conclusions: Our genome-wide systematic analysis of mature sequences, genomic locations, evolutionary sequence conservation, and tissue expression profiles of the zebra finch miRNA repertoire provides a valuable resource to the research community. Our analysis also reveals a miRNA-mediated mechanism that potentially regulates sex-biased gene expression in avian species.

Show MeSH
Related in: MedlinePlus