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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.

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Length distributions of loops and their relevant evolutionary tree.(A) Length distribution of the let-7 loop among different animal species; (B) length distribution of loops in homologous miRNAs within the let-7 family across different animal species; and (C) length distribution of homologous hsa-let-7 loops and relevant evolutionary tree.
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pone-0113042-g003: Length distributions of loops and their relevant evolutionary tree.(A) Length distribution of the let-7 loop among different animal species; (B) length distribution of loops in homologous miRNAs within the let-7 family across different animal species; and (C) length distribution of homologous hsa-let-7 loops and relevant evolutionary tree.

Mentions: Based on the whole let-7 population, changes in length distribution across different species were found to be significant (F = 19.14, P<0.0001, Figure 3A). The longest average loop length was found in vertebrates (28.13±4.66 nts), followed by those in urochordates (27.36±9.78 nts), which were longer loop sequences than those found in other metazoans (Figure 3A). Each member in the let-7 gene family showed an inconsistent length distribution (Figure 3), despite being homologous miRNAs with higher sequence similarity. Specifically, let-7a (25.12±3.99 nts), let-7c (22.03±2.81 nts) and let-7e (24.17±3.21 nts) had shorter length distributions than other homologous miRNAs (from 28.12±4.87 nts to 35.25±1.50 nts) (F = 39.97, P<0.0001, Figure 3B). To further examine potential relationships between length distributions and evolutionary patterns, hsa-let-7 family loop sequences were analyzed. Loop sequences from multicopy pre-miRNAs showed larger divergence lengths, with these relevant loop sequences located in different evolutionary clusters (Figure 3C and Figure S1C in File S1). Larger genetic distances were noted in homologous miRNAs, with shorter loops from the let-7a-2, let-7c and let-7e genes located in a single cluster (Figure 3C and Figure S1C 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)

Length distributions of loops and their relevant evolutionary tree.(A) Length distribution of the let-7 loop among different animal species; (B) length distribution of loops in homologous miRNAs within the let-7 family across different animal species; and (C) length distribution of homologous hsa-let-7 loops and relevant evolutionary tree.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0113042-g003: Length distributions of loops and their relevant evolutionary tree.(A) Length distribution of the let-7 loop among different animal species; (B) length distribution of loops in homologous miRNAs within the let-7 family across different animal species; and (C) length distribution of homologous hsa-let-7 loops and relevant evolutionary tree.
Mentions: Based on the whole let-7 population, changes in length distribution across different species were found to be significant (F = 19.14, P<0.0001, Figure 3A). The longest average loop length was found in vertebrates (28.13±4.66 nts), followed by those in urochordates (27.36±9.78 nts), which were longer loop sequences than those found in other metazoans (Figure 3A). Each member in the let-7 gene family showed an inconsistent length distribution (Figure 3), despite being homologous miRNAs with higher sequence similarity. Specifically, let-7a (25.12±3.99 nts), let-7c (22.03±2.81 nts) and let-7e (24.17±3.21 nts) had shorter length distributions than other homologous miRNAs (from 28.12±4.87 nts to 35.25±1.50 nts) (F = 39.97, P<0.0001, Figure 3B). To further examine potential relationships between length distributions and evolutionary patterns, hsa-let-7 family loop sequences were analyzed. Loop sequences from multicopy pre-miRNAs showed larger divergence lengths, with these relevant loop sequences located in different evolutionary clusters (Figure 3C and Figure S1C in File S1). Larger genetic distances were noted in homologous miRNAs, with shorter loops from the let-7a-2, let-7c and let-7e genes located in a single cluster (Figure 3C and Figure S1C 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