Paper summarized - Principles of microRNA regulation of a human cellular signaling network

Principles of microRNA regulation of a human cellular signaling network
Qinghua Cui, Zhenbao Yu, Enrico O Purisima and Edwin Wang

What are microRNAs?

• ~22nucleotide long non-coding RNAs
• responsible for RNA-based gene regulation
• act as post transcriptional and translational regulators
• base-pair with target mRNAs
• ~1% of predicted genes in human genome
• BUT Regulate 10–30% of genes
• Targets
  
  • signaling proteins
  • enzymes
  • transcription factors

It is unclear if and how miRNAs might orchestrate their regulation of cellular signaling networks and how regulation of these networks might contribute to the biological functions of miRNAs.

What are signalling networks?
These make decisions about whether to grow, differentiate, move or die. Their components are Proteins. They are represented as graphs where the nodes represent the proteins and the links between the nodes represent the interactions between the proteins.

Hypothesis paper is based on
Role of miRNAs in strength and specificity of signaling networks through direct control of proteins at post-transcriptional and translational levels.

Signaling network used:
Signal transduction processes from multiple cell surface receptors to various cellular machines in a mammalian hippocampal CA1 neuron consisting of:
540 nodes
1258 links
-689 activating (positive) links
-306 inhibitory (negative) links
-263 neutral (protein interactions)

Results stated (Glossary for the terms given below)

• MiRNAs more frequently target network downstream signaling components than ligands and cell surface receptors



• MiRNAs preferentially target the downstream components of the adaptors, which have potential to recruit more downstream components


• MiRNAs more frequently target positively linked network motifs


• MiRNAs avoid targeting common components of cellular machines in the network

Glossary

1. adaptor proteins: The function of these proteins is recruiting downstream signaling components to the vicinity of receptors. It invloves no enzyme activity – they physically interact with upstream and downstream signaling proteins
   
2. network motif: A complex signaling network can be broken down into distinct regulatory patterns, or network motifs, typically comprised of three to four interacting components capable of signal processing. The function of a motif also depends on whether the links are positive or negative.
3. scaffold proteins: Unlike adaptors, scaffold proteins do not directly activate or inhibit other proteins but provide regional organization for activation or inhibition between other proteins.
4. functional modules: represent a set of proteins that are always present in various cellular conditions.