Article

The Sequence Structures of Human MicroRNA Molecules and Their Implications.

Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
PLoS ONE (Impact Factor: 3.53). 01/2013; 8(1):e54215. DOI: 10.1371/journal.pone.0054215
Source: PubMed

ABSTRACT The count of the nucleotides in a cloned, short genomic sequence has become an important criterion to annotate such a sequence as a miRNA molecule. While the majority of human mature miRNA sequences consist of 22 nucleotides, there exists discrepancy in the characteristic lengths of the miRNA sequences. There is also a lack of systematic studies on such length distribution and on the biological factors that are related to or may affect this length. In this paper, we intend to fill this gap by investigating the sequence structure of human miRNA molecules using statistics tools. We demonstrate that the traditional discrete probability distributions do not model the length distribution of the human mature miRNAs well, and we obtain the statistical distribution model with a decent fit. We observe that the four nucleotide bases in a miRNA sequence are not randomly distributed, implying that possible structural patterns such as dinucleotide (trinucleotide or higher order) may exist. Furthermore, we study the relationships of this length distribution to multiple important factors such as evolutionary conservation, tumorigenesis, the length of precursor loop structures, and the number of predicted targets. The association between the miRNA sequence length and the distributions of target site counts in corresponding predicted genes is also presented. This study results in several novel findings worthy of further investigation that include: (1) rapid evolution introduces variation to the miRNA sequence length distribution; (2) miRNAs with extreme sequence lengths are unlikely to be cancer-related; and (3) the miRNA sequence length is positively correlated to the precursor length and the number of predicted target genes.

0 Bookmarks
 · 
52 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Synonymous codon changes, which do not alter protein sequence, were previously thought to have no functional consequence. Although this concept has been overturned in recent years, there is no unique mechanism by which these changes exert biological effects. A large repertoire of both experimental and bioinformatic methods has been developed to understand the effects of synonymous variants. Results from this body of work have provided global insights into how biological systems exploit the degeneracy of the genetic code to control gene expression, protein folding efficiency, and the coordinated expression of functionally related gene families. Although it is now clear that synonymous variants are important in a variety of contexts, from human disease to the safety and efficacy of therapeutic proteins, there is no clear consensus on the approaches to identify and validate these changes. Here, we review the diverse methods to understand the effects of synonymous mutations.
    Trends in genetics : TIG. 06/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen + ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin + UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p < 0.05) and an impaired platelet aggregation response to ADP (p < 0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established.
    Platelets 04/2014; · 2.24 Impact Factor

Full-text

View
0 Downloads
Available from

Similar Publications