miR-375

  Introduction
 
   miR-375, an islet specific microRNA, was first discovered by by a team of researchers from Rockefeller University, Lund University (Sweden), New York University, and Oxford University and published at Nature in Nov. 2004. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si)RNA mimicked the effects of miR-375 on glucosestimulated insulin secretion and exocytosis. Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes [1].

Panel 1. Translational repression of myotrophin by miR-375. - (a) The dsDNA gene for myotrophin (Mtpn) and its transcribed mRNA, showing both the 5?unstranlated region (UTF) and open reading frame (ORF). (b) In the wild type setting, the single-stranded miR-375 microRNA anneals to a portion of the 5?UTF and represses downstream translation. (c) Upon the addition of small interfering (si) RNAs (siRNA), specifically ones (si-375) that are sequence analogues to miR-375, the effective concentration of miR-375 increases and anneals to more Mtpn 5?UTFs, further repressing Mtpn expression. However, when an antisense RNA (antisense to miR-375) is added, it anneals to miR-375 and prevents it from annealing to the 5?UTR, thereby enhancing Mtpn expression. Mtpn is a component of insulin exocytosis.
(Source: Beta Cell Biology Consortium  http://www.betacell.org/content/articles/articlepanel.php?aid=7&pid=1)

 


Query Summary

Query Type Family Accession Family ID miRBase ID1 miRBase ID2 # of members
mir-375 family MIPF0000114 mir-375 . . 8


microRNA family : mir-375 [MIPF0000114] miRBase

ID Accession Chromosome Start End Strand Genome MIRANDA1 TARGETSCAN1 MIRANDA2 TARGETSCAN2 Structure
dre-mir-375-1 MI0002072 6
13423599
13423678
-
Coordinate dre-miR-375       dre-mir-375-1
dre-mir-375-2 MI0002073 9
10232524
10232606
-
Coordinate dre-miR-375       dre-mir-375-2
fru-mir-375 MI0003419 scaffold_3113
scaffold_83
9349
92347
9425
92423
+
+
Coordinate fru-miR-375       fru-mir-375
gga-mir-375 MI0003705 7
23117692
23117756
+
Coordinate gga-miR-375 gga-miR-375     gga-mir-375
hsa-mir-375 MI0000783 2
219574611
219574674
-
Coordinate hsa-miR-375 hsa-miR-375     hsa-mir-375
mdo-mir-375 MI0005327 7
175492651
175492713
+
Coordinate mdo-miR-375       mdo-mir-375
mmu-mir-375 MI0000792 1
74833865
74833928
-
Coordinate mmu-miR-375 mmu-miR-375     mmu-mir-375
tni-mir-375 MI0003420 2
15358681
15358757
-
Coordinate tni-miR-375       tni-mir-375

microRNA stem-loop sequence alignment
CLUSTAL W (1.83) multiple sequence alignment

hsa-mir-375 --------CCCCGCGACGAGCCCCUCGCACAA-ACCGG-ACCUGAGC--GUUUUGUUCGU
mmu-mir-375 --------CCCCGCGACGAGCCCCUCGCACAA-ACCGG-ACCUGAGC--GUUUUGUUCGU
mdo-mir-375 ---------CCCGCGCCGAGCCCCUCGCACAA-ACCGG-ACCUGAGC--GUUUUGUUCGU
gga-mir-375 --------CCUGGCGUCGAGCCCCACGUGCAAGACCUG-ACCUGAAC--GUUUUGUUCGU
fru-mir-375 UGUACUUGCUUCACGUUGAGCCUCACGCACAAUACCUGAAGAUGAA---GUUUUGUUCGU
tni-mir-375 UGUACUUGCUUCACGUUGAGCCUCACGCACAAUACCUGAAGAUGAA---GUUUUGUUCGU
dre-mir-375-1 UGCACUUGCUUUACGUUGAGCCACACGCACAAUACAUGUGGAUUCA---GUUUUGUUCGU
dre-mir-375-2 UGUACUUGUCUCACGUUGAGCCACACGCACAAUGCCUGCAGAUGAAAGGGUUUUGUUCGU
** ***** * ** *** * * * ***********

hsa-mir-375 UCGGCUCGCGUGAGGC-------
mmu-mir-375 UCGGCUCGCGUGAGGC-------
mdo-mir-375 UCGGCUCGCGUGAGGC-------
gga-mir-375 UCGGCUCGCGUUAGGC-------
fru-mir-375 UCGGCUCGCGUUAUGCAGGU---
tni-mir-375 UCGGCUCGCGUUAUGCAGGU---
dre-mir-375-1 UCGGCUCGCGUUAAGCAAGUGCA
dre-mir-375-2 UCGGCUCGCGUUACGCAGAUGCA
*********** * **



Conserved Secondary Structure Prediction - By RNAalifold in ViennaRNA package

________CCUCACGUCGAGCCCCACGCACAAUACCUG_ACAUGAAC__GUUUUGUUCGUUCGGCUCGCGUUAGGC_______
............(((.((((((...((.((((.((..............)).)))).))...)))))))))............ (-17.55 = -16.83 + -0.72)
............(((.((((((...((.((((.((..............)).)))).))...)))))))))............ [-17.96]
frequency of mfe structure in ensemble 0.507898