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Genetic analysis of loop sequences in the let-7 gene family reveal a relationship between loop evolution and multiple isomiRs.

Liang T, Yang C, Li P, Liu C, Guo L - PLoS ONE (2014)

Bottom Line: Examination of these loop sequence length distributions, in addition to phylogenetic tree construction, implicated loop sequences as the main evolutionary drivers in miRNA genes.Moreover, loops from relevant clustered miRNA gene families showed varying length distributions and higher levels of nucleotide divergence, even between homologous pre-miRNA loops.Overall, this study provides further insight into miRNA processing and maturation and further enriches our understanding of miRNA biogenesis.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210023, China.

ABSTRACT
While mature miRNAs have been widely studied, the terminal loop sequences are rarely examined despite regulating both primary and mature miRNA functions. Herein, we attempted to understand the evolutionary pattern of loop sequences by analyzing loops in the let-7 gene family. Compared to the stable miRNA length distributions seen in most metazoans, higher metazoan species exhibit a longer length distribution. Examination of these loop sequence length distributions, in addition to phylogenetic tree construction, implicated loop sequences as the main evolutionary drivers in miRNA genes. Moreover, loops from relevant clustered miRNA gene families showed varying length distributions and higher levels of nucleotide divergence, even between homologous pre-miRNA loops. Furthermore, we found that specific nucleotides were dominantly distributed in the 5' and 3' terminal loop ends, which may contribute to the relatively precise cleavage that leads to a stable isomiR expression profile. Overall, this study provides further insight into miRNA processing and maturation and further enriches our understanding of miRNA biogenesis.

Show MeSH
The distribution of the let-7 family among metazoan animals.The let-7 gene was named and homologous miRNAs were further found and named. These miRNA names were consistent with the current annotations in the miRBase database. “2*” indicates that there are two genes, rno-mir-3596b and rno-mir-3596d, and not two pre-miRNAs for the mature miRNA.
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pone-0113042-g001: The distribution of the let-7 family among metazoan animals.The let-7 gene was named and homologous miRNAs were further found and named. These miRNA names were consistent with the current annotations in the miRBase database. “2*” indicates that there are two genes, rno-mir-3596b and rno-mir-3596d, and not two pre-miRNAs for the mature miRNA.

Mentions: Let-7 gene family members have been found in 75 metazoan animal species (Figure 1). Multiple homologous miRNA genes, some being multicopy pre-miRNAs, were more prevalent in vertebrates and urochordates, while single miRNA genes were more common in other metazoan species (Figure 1). Among these miRNAs, let-7a showed higher pre-miRNA multicopy numbers (1–7) relative to other homologous miRNAs. Although these multicopy pre-miRNAs could generate the same let-7a-5p sequences, their loop sequences showed larger genetic distances (Figure S1 in File S1). Phylogenetic tree construction showed that the pre-miRNA multicopy loop sequences may be divided into two clusters based on loop and pre-miRNA sequences, with distribution differences noted (Figure S1 in File S1).


Genetic analysis of loop sequences in the let-7 gene family reveal a relationship between loop evolution and multiple isomiRs.

Liang T, Yang C, Li P, Liu C, Guo L - PLoS ONE (2014)

The distribution of the let-7 family among metazoan animals.The let-7 gene was named and homologous miRNAs were further found and named. These miRNA names were consistent with the current annotations in the miRBase database. “2*” indicates that there are two genes, rno-mir-3596b and rno-mir-3596d, and not two pre-miRNAs for the mature miRNA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232593&req=5

pone-0113042-g001: The distribution of the let-7 family among metazoan animals.The let-7 gene was named and homologous miRNAs were further found and named. These miRNA names were consistent with the current annotations in the miRBase database. “2*” indicates that there are two genes, rno-mir-3596b and rno-mir-3596d, and not two pre-miRNAs for the mature miRNA.
Mentions: Let-7 gene family members have been found in 75 metazoan animal species (Figure 1). Multiple homologous miRNA genes, some being multicopy pre-miRNAs, were more prevalent in vertebrates and urochordates, while single miRNA genes were more common in other metazoan species (Figure 1). Among these miRNAs, let-7a showed higher pre-miRNA multicopy numbers (1–7) relative to other homologous miRNAs. Although these multicopy pre-miRNAs could generate the same let-7a-5p sequences, their loop sequences showed larger genetic distances (Figure S1 in File S1). Phylogenetic tree construction showed that the pre-miRNA multicopy loop sequences may be divided into two clusters based on loop and pre-miRNA sequences, with distribution differences noted (Figure S1 in File S1).

Bottom Line: Examination of these loop sequence length distributions, in addition to phylogenetic tree construction, implicated loop sequences as the main evolutionary drivers in miRNA genes.Moreover, loops from relevant clustered miRNA gene families showed varying length distributions and higher levels of nucleotide divergence, even between homologous pre-miRNA loops.Overall, this study provides further insight into miRNA processing and maturation and further enriches our understanding of miRNA biogenesis.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210023, China.

ABSTRACT
While mature miRNAs have been widely studied, the terminal loop sequences are rarely examined despite regulating both primary and mature miRNA functions. Herein, we attempted to understand the evolutionary pattern of loop sequences by analyzing loops in the let-7 gene family. Compared to the stable miRNA length distributions seen in most metazoans, higher metazoan species exhibit a longer length distribution. Examination of these loop sequence length distributions, in addition to phylogenetic tree construction, implicated loop sequences as the main evolutionary drivers in miRNA genes. Moreover, loops from relevant clustered miRNA gene families showed varying length distributions and higher levels of nucleotide divergence, even between homologous pre-miRNA loops. Furthermore, we found that specific nucleotides were dominantly distributed in the 5' and 3' terminal loop ends, which may contribute to the relatively precise cleavage that leads to a stable isomiR expression profile. Overall, this study provides further insight into miRNA processing and maturation and further enriches our understanding of miRNA biogenesis.

Show MeSH