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Chromatin Structure Regulates pre-mRNA Processing02:41

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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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MicroRNAs01:22

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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Regulation of Expression Occurs at Multiple Steps02:24

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal

J M Robinson1, W A Henderson2

  • 1Digestive Disorder Unit, Biobehavioral Branch, Division of Intramural Research, National Institute of Nursing Research, NIH, DHHS, Bethesda, MD, USA. jeff.robinson.evol@gmail.com.

BMC Research Notes
|January 14, 2018
PubMed
Summary
This summary is machine-generated.

This study introduces a network model to uncover microRNA-mRNA interactions that regulate intestinal barrier function. The model identified key genes like c-MYC and Cyclin D involved in cellular proliferation and cancer.

Keywords:
Adherens junctionBipartite affiliation networkCompeting endogenous RNAEpithelial barrier functionIntestinal epithelial cellsKEGG pathway databaseMicroRNARac–Rock–Rho signalingRegulation of actin cytoskeletonTight junction

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Area of Science:

  • Molecular Biology
  • Bioinformatics
  • Systems Biology

Background:

  • Intestinal epithelial barrier function is crucial for homeostasis and is regulated by complex molecular networks.
  • Dysregulation of this barrier is linked to inflammation, osmotic issues, and cancer development.
  • MicroRNA-mRNA interactions are key regulators but are challenging to predict and validate.

Purpose of the Study:

  • To develop a computational method for identifying hypothetical mRNA-miRNA interaction networks.
  • To analyze these networks in the context of intestinal epithelial barrier regulation.
  • To identify specific genes and microRNAs involved in cellular proliferation and cancer.

Main Methods:

  • Utilized functional-molecular databases (KEGG, miRWalk2.0) to generate mRNA-miRNA interaction lists.
  • Developed a network modeling approach using R-code for data analysis and visualization.
  • Integrated RNA expression data from Nanostring nCounter® system with network analysis.

Main Results:

  • A novel network model was created to identify co-regulatory motifs in mRNA-miRNA interactions.
  • A specific sub-network was identified, highlighting shared targeting microRNAs.
  • Key genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D, were pinpointed within this network.

Conclusions:

  • The developed network model effectively identifies hypothetical mRNA-miRNA interactions regulating epithelial function.
  • This approach aids in understanding the complexity of competing-endogenous RNA networks.
  • The findings highlight potential therapeutic targets within cancer-related gene networks.