PMID- 20920310
OWN - NLM
STAT- MEDLINE
DCOM- 20101227
LR  - 20211020
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 11
DP  - 2010 Oct 1
TI  - A potential role for intragenic miRNAs on their hosts' interactome.
PG  - 533
LID - 10.1186/1471-2164-11-533 [doi]
AB  - BACKGROUND: miRNAs are small, non-coding RNA molecules that mainly act as 
      negative regulators of target gene messages. Due to their regulatory functions, 
      they have lately been implicated in several diseases, including malignancies. 
      Roughly half of known miRNA genes are located within previously annotated 
      protein-coding regions ("intragenic miRNAs"). Although a role of intragenic 
      miRNAs as negative feedback regulators has been speculated, to the best of our 
      knowledge there have been no conclusive large-scale studies investigating the 
      relationship between intragenic miRNAs and host genes and their pathways. 
      RESULTS: miRNA-containing host genes were three times longer, contained more 
      introns and had longer 5' introns compared to a randomly sampled gene cohort. 
      These results are consistent with the observation that more than 60% of intronic 
      miRNAs are found within the first five 5' introns. Host gene 3'-untranslated 
      regions (3'-UTRs) were 40% longer and contained significantly more 
      adenylate/uridylate-rich elements (AREs) compared to a randomly sampled gene 
      cohort. Coincidentally, recent literature suggests that several components of the 
      miRNA biogenesis pathway are required for the rapid decay of mRNAs containing 
      AREs. A high-confidence set of predicted mRNA targets of intragenic miRNAs also 
      shared many of these features with the host genes. Approximately 20% of 
      intragenic miRNAs were predicted to target their host mRNA transcript. Further, 
      KEGG pathway analysis demonstrated that 22 of the 74 pathways in which host genes 
      were associated showed significant overrepresentation of proteins encoded by the 
      mRNA targets of associated intragenic miRNAs. CONCLUSIONS: Our findings suggest 
      that both host genes and intragenic miRNA targets may potentially be subject to 
      multiple layers of regulation. Tight regulatory control of these genes is likely 
      critical for cellular homeostasis and absence of disease. To this end, we 
      examined the potential for negative feedback loops between intragenic miRNAs, 
      host genes, and miRNA target genes. We describe, how higher-order miRNA feedback 
      on hosts' interactomes may at least in part explain correlation patterns observed 
      between expression of host genes and intragenic miRNA targets in healthy and 
      tumor tissue.
FAU - Hinske, Ludwig Christian G
AU  - Hinske LC
AD  - Department of Anaesthesiology, Clinic of the University of Munich, Munich, 
      Germany. ludwig.hinske@med.uni-muenchen.de
FAU - Galante, Pedro A F
AU  - Galante PA
FAU - Kuo, Winston P
AU  - Kuo WP
FAU - Ohno-Machado, Lucila
AU  - Ohno-Machado L
LA  - eng
GR  - U54 HL108460/HL/NHLBI NIH HHS/United States
GR  - U54HL108460/HL/NHLBI NIH HHS/United States
GR  - D43 TW001279/TW/FIC NIH HHS/United States
GR  - D43TW007015/TW/FIC NIH HHS/United States
GR  - UL1 RR025758/RR/NCRR NIH HHS/United States
GR  - D43 TW007015/TW/FIC NIH HHS/United States
GR  - D43 TW007015-08/TW/FIC NIH HHS/United States
GR  - R01 LM009520/LM/NLM NIH HHS/United States
GR  - R01 LM009520-04/LM/NLM NIH HHS/United States
GR  - U54 HL108460-01/HL/NHLBI NIH HHS/United States
GR  - D43 TW001279-04S1/TW/FIC NIH HHS/United States
GR  - UL1 RR 025758/RR/NCRR NIH HHS/United States
GR  - R01LM009520/LM/NLM NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101001
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Animals
MH  - Bias
MH  - Carcinoma, Non-Small-Cell Lung/genetics
MH  - Conserved Sequence/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Genome, Human/genetics
MH  - Humans
MH  - Introns/genetics
MH  - Lung Neoplasms/genetics
MH  - MicroRNAs/classification/genetics/*metabolism
MH  - Open Reading Frames/*genetics
PMC - PMC3091682
EDAT- 2010/10/06 06:00
MHDA- 2010/12/28 06:00
PMCR- 2010/10/01
CRDT- 2010/10/06 06:00
PHST- 2010/04/19 00:00 [received]
PHST- 2010/10/01 00:00 [accepted]
PHST- 2010/10/06 06:00 [entrez]
PHST- 2010/10/06 06:00 [pubmed]
PHST- 2010/12/28 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 1471-2164-11-533 [pii]
AID - 10.1186/1471-2164-11-533 [doi]
PST - epublish
SO  - BMC Genomics. 2010 Oct 1;11:533. doi: 10.1186/1471-2164-11-533.