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PLoS One. 2014 May 13;9(5):e96498. doi: 10.1371/journal.pone.0096498. eCollection 2014.

Diversity and expression of microRNAs in the filarial parasite, Brugia malayi.

Author information

1
Division of RNA Biology, New England Biolabs, Ipswich, Massachusetts, United States of America; Division of Parasitology, New England Biolabs, Ipswich, Massachusetts, United States of America.
2
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
3
Division of Parasitology, New England Biolabs, Ipswich, Massachusetts, United States of America.
4
Division of RNA Biology, New England Biolabs, Ipswich, Massachusetts, United States of America.
5
Division of RNA Biology, New England Biolabs, Ipswich, Massachusetts, United States of America; Cancer Research Center of Lyon, Lyon, France.

Abstract

Human filarial parasites infect an estimated 120 million people in 80 countries worldwide causing blindness and the gross disfigurement of limbs and genitals. An understanding of RNA-mediated regulatory pathways in these parasites may open new avenues for treatment. Toward this goal, small RNAs from Brugia malayi adult females, males and microfilariae were cloned for deep-sequencing. From ∼ 30 million sequencing reads, 145 miRNAs were identified in the B. malayi genome. Some microRNAs were validated using the p19 RNA binding protein and qPCR. B. malayi miRNAs segregate into 99 families each defined by a unique seed sequence. Sixty-one of the miRNA families are highly conserved with homologues in arthropods, vertebrates and helminths. Of those miRNAs not highly conserved, homologues of 20 B. malayi miRNA families were found in vertebrates. Nine B. malayi miRNA families appear to be filarial-specific as orthologues were not found in other organisms. The miR-2 family is the largest in B. malayi with 11 members. Analysis of the sequences shows that six members result from a recent expansion of the family. Library comparisons found that 1/3 of the B. malayi miRNAs are differentially expressed. For example, miR-71 is 5-7X more highly expressed in microfilariae than adults. Studies suggest that in C.elegans, miR-71 may enhance longevity by targeting the DAF-2 pathway. Characterization of B. malayi miRNAs and their targets will enhance our understanding of their regulatory pathways in filariads and aid in the search for novel therapeutics.

PMID:
24824352
PMCID:
PMC4019659
DOI:
10.1371/journal.pone.0096498
[Indexed for MEDLINE]
Free PMC Article

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