RNAs and MicroRNAs: Synthesis, Mechanism & Function

Heart, Immune | March 9, 2018 | Author: Naturopath

Immune, heart disease, cancer

RNAs and MicroRNAs: Synthesis, Mechanism & Function

RNAs and microRNAs are hitting the headlines as the potential underlying mechanisms behind diseases and their cures. If zooming in this close to our biology gives you vertigo, don't worry –

We'll keep it simple

RNA

RNARNA and DNA are related. While DNA is a double-strand helix, RNA has only one strand and consists of a relatively short chain of nucleotides that can twist and bend upon itself.

RNA is created by DNA on an as-needed basis.
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But it's weird that DNA gets all the attention – RNAs make up 5% of the weight of a human cell, while DNA only contributes 1%.

While DNA is used for long-term storage of genetic material, RNA is used to transfer the genetic code from the DNA in the nucleus of a cell to the “ribosomes” in another area of the cell. The ribosomes then make proteins based on the information provided by the RNA. This whole process means that the DNA can stay safe and cozy in the nucleus, but still get its message to the ribosomes. RNA is kind of like its gopher.

Without RNA, proteins could never be made. [1]

Quick recap of what proteins are needed for

Uh, everything. Enzymes, detoxification, cellular structure, receptors, hormones, fluids, blood, neurotransmitters, immune function, literally the whole body!

There are four types of RNAs involved in protein synthesis:

 mRNA: Messenger RNA, which carries codes from DNA to the ribosome (a ribosomes is a complex molecular machine, found within all living cells, that serves as the site of biological protein synthesis. Ribosomes link amino acids together in the order specified by messenger RNA molecules).[10]

tRNA: Transfer RNA, which brings extra amino acids to the ribosome to help with protein synthesis

rRNA: Ribosomal RNA, which (along with certain proteins) forms the ribosome itself

snRNA: Small nuclear RNA, which forms complexes for RNA to be created by DNA

When there is a problem with our RNA, such as a mutation or “silencing” (take note), the proteins it creates (or fails to create) can cause dysfunction and disease. [9]

MicroRNAs

Let's zoom in even further.

MicroRNAs are – you guessed it – tiny RNAs. To confuse things a little, “microRNAs” is often shortened to “mirRNAs” which is annoyingly close to “mRNAs”. MicroRNAs are only 21 – 25 nucleotides in length, but they pack a punch. They don't code proteins like RNA does, but they regulate what RNA can and can't do. MicroRNA influences gene expression by stopping RNAs from moving information from the DNA to the ribosomes. [8]

MicroRNAs “silence”  RNAs by:

·       Cleaving RNA into two pieces. Nasty!

·       Destabilise the RNA by shortening it.

·       Influencing the ribosomes and causing less efficient translation of the RNA into proteins. [8]

Like all things at this level of biology, the synthesis of microRNAs is very complex. To simplify it as much as we can, microRNA is transcribed within the nucleus as “primary-miRNA”, then transported to the cytoplasm for processing into microRNA. There are about 100 steps in between, and the complexity of the whole process is a clue that the types and numbers of microRNAs created is highly regulated for a reason --- they have a huge impact on our health.

By influencing RNAs, microRNAs are involved in

  • MicroRNAsBlood cell differentiation
  • Cell proliferation, growth and death
  • Inflammation
  • Tissue health
  • Fat metabolism
  • Insulin secretion
  • Neural pathways
  • Immune responses
  • Cardiac and skeletal muscle development
  • Cholesterol metabolism [1]

The human genome codes for over 1,000 microRNAs, but did you know that food also contains microRNAs... and that they can influence our gene expression?

A 2011 study discovered that microRNA found in rice is able to survive digestion, be transported to the blood, and even affect gene expression like our own microRNA would. The particular microRNA in the study was shown to increase LDL (“bad”) cholesterol levels. Seriously! [3]

Like all processes in the human body, microRNAs can be “good” or “bad”, depending on the situation. With such a huge influence over our physiology, microRNA likely has a role in every disease, but here are three major areas of research:

MicroRNA in Heart Disease

MicroRNA-712 has been identified as a biomarker for atherosclerosis – the more microRNA-712 present, the more likely atherosclerosis will develop, or has developed.

Blood vessels contain an extracellular matrix (ECM), a type of structural tissue made of collagen and elastin, which keeps the vessel's shape and allows it to spring back after being stretched.

IMicroRNA in Heart Diseasen atherosclerosis, the ECM is degraded, plaques are subject to rupturing, and the artery wall becomes rigid and easily blocked [2].

Different microRNAs have been shown to speed up or slow down this destruction of the arterial extracellular matrix:

  • MircoRNA-155 and microRNA-712 modulate genes involved in inflammation, causing the destruction of artery walls.
  • MicroRNA-145 controls genes for smooth muscle cells and promotes lesions.
  • MicroRNA-136 boosts signals for repair! Finally, a good guy!

MicroRNA in Viruses

Viruses are capable of regulating the expression of host microRNA for their own benefit. For example, Epstein Barr virus up-regulates the expression of microRNA-155 (the same nasty guy that contributes to atherosclerosis) to prevent the death of cells that it has infected. [4]

But it's not all bad news. Cellular microRNA is able to infiltrate viruses and modulate their growth, too. MicroRNA-150 was shown to restrict the replication of viruses such as HIV-1 [4].

MicroRNA in Cancer

MicroRNA in CancerDisturbance to microRNA expression and function is a suspected cause of cancer. Hundreds of strains of microRNA have been identified as contributing to tumour growth and unrestricted cell growth. In particular, microRNA-222 helps cancerous cells to evade growth suppressor signals and send their own signals to promote further growth of a tumour, while that notorious microRNA-155 promotes cell growth.

Don't worry, some “good guy” microRNAs are at play here, too. MicroRNA-21 has a strong anti-inflammatory action that may also help to curb unregulated growth in cancer. [7]

Foods & Nutrients for MicroRNA

Polyphenols from Pomegranates

In breast cancer cells, polyphenols from pomegranates have been shown to decrease microRNA-155 – the “bad guy” that can cause major inflammation and excessive cell growth. They may also help to lower the atherosclerosis risk associated with high levels of microRNA-712 [7].

Resveratrol from Grapes

Studies have shown that resveratrol fro grapes is able to modulate the expression of microRNA. In particular, resveratrol or grape extract may be able to:

Down-regulate the expression of inflammatory cytokines by switching off microRNA-712.

Decrease inflammation and protect against cardiovascular disease, hypertension and cancer by decreasing microRNA-155 expression.

Reduce hypertension and cancer cell proliferation by up-regulating anti-inflammatory microRNA-21. [5]

 

Vitamin D

Vitamin D is involved in all stages of gene transcription and expression, and can down-regulate inflammatory microRNA-155 and boost microRNA-136. This combination may protect against cancer and cardiovascular disease. It can even help to fight off viral infection by promoting microRNA-150 and microRNA-142 [5]. Time to get some sun!
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Folate

Folate has been found to modulate the types of microRNAs expressed by RNAs.

One study showed that people with low levels of folate had higher amounts of microRNA-222 – the type that boosts tumour growth and cancer cell signalling.

By boosting folate in the diet, they were able to lower their levels of that microRNA and boost anti-cancer microRNAs instead! [6]

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References

[1] Wahid, F., et al. (2010) MicroRNAs: Synthesis, mechanism, function, and recent clinical trials. Biochimica et Biophysica Acta, 1803:11, 1231 – 1243. https://www.sciencedirect.com/science/article/pii/S0167488910001837#bb0060

[2] Katsuda, S. & Kaji, T. (2003) Atherosclerosis and extracellular matrix. J Atherosclerosis Thromb., 10:5, 267 – 274. https://www.ncbi.nlm.nih.gov/pubmed/14718743

[3] Zhang, L., et al. (2012) Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Research, 22, 107 – 126. https://www.nature.com/articles/cr2011158

[4] Grassmann, R. & Jeang, K. (2008) The roles of microRNAs in mammalian virus infection. Biochim Biophys Acta. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2641032/

[5] Quintanilha, B. J., et al. (2017) Nutrimiromics: Role of microRNAs and Nutrition in Modulating Inflammation and Chronic Diseases. 9:11, 1168. http://www.mdpi.com/2072-6643/9/11/1168/htm

[6] Marsit, C. J., et al. (2006) MicroRNA Responses to Cellular Stress. Cancer Research. http://cancerres.aacrjournals.org/content/66/22/10843.long

[7] Ross, S. A. & Davis, C. D. (2014) The emerging role of microRNAs and nutrition in modulating health and disease. Annu Rev Nutr., 34, 305 – 336. https://www.ncbi.nlm.nih.gov/pubmed/25033062

[8] Brennecke, J., et al. (2005) Principles of microRNA-target recognition. PLoS Bio., 3:3, e85. https://www.ncbi.nlm.nih.gov/pubmed/15723116

[10]https://en.wikipedia.org/wiki/Ribosome

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