Cell cycle-regulated genes and mRNA

Question

I am a mathematician and my knowledge about biology is close to zero. I am reading a bioinformatics paper and I would like to understand a bit more about the biology task they are talking about. I cite here the first paragraph of the paper:

The identification of cell cycle-regulated genes through the cyclicity of messenger RNAs in genome-wide studies is a difficult task due to the presence of internal and external noise in microarray data. Moreover, the analysis is also complicated by the loss of synchrony occurring in cell cycle experiments, which often results in additional background noise.
[De Santis, Marianna, et al. "Combining optimization and machine learning techniques for genome-wide prediction of human cell cycle-regulated genes." Bioinformatics (2013): btt671.]

I've searched online for some explanation of this topic and I understand that cell-cycle is a set of events that cells go through for duplicating themselves. I also understand that there are some molecules that are responsible for the regulation of the cell cycle. I know that mRNA is a class of nucleic acid that is responsible for transferring the informations from the DNA inside the nucleus to the ribosomes in order begin the amino acids synthesis. Microarrays are matrices obtained by DNA sequences inside some chip.

What is the cyclicity of mRNA? How is it related to the cell cycle?

_{I just need a very simple explanation, without any detail, as it is not my field but I am concerned to understand the background.}

Answer 1

It is assumed that in order for a cell to divide it must progress through a series of gradual stages. At each of these phases certain proteins have to be manufactured through mRNA and/or modified post-transcriptionally in order to serve an specific proliferative or anti-proliferative role, which overall eventually orchestrates the transit to the subsequent stage.

Conventionally the cell cycle is comprised of 3 "interphase" stages prior to execution of Mitosis itself: G1 (growth, metabolically active), S (synthesis of DNA to duplicate genetic material in preparation for its splitting into two daughter cells), and G2 (gap phase where a numerous of quality control checks are undertaken in the form of surveillance of the newly produced DNA for example to ensure viability of the progenies).

Under these premises, the protein content of a cell at an specific phase is expected to cycle or oscillate in accordance with its requirements, and this is linked to mRNA cyclicity as the most direct responsible process for modulation of protein abundance. It is then related to the cell cycle in the sense that in order to transit from the G1 phase for instance, proteins involved in DNA synthesis will need to be produced, and thus protein factors released for the transcription of those certain mRNAs to take place.

Experimentally such dissection of cell cycle-regulated genes is tricky. Extracting mRNA from pure sub-populations of cells at specific stages of cell division is challenging as the isolation of such cell sub-populations is normally through chemical enrichments and sub-optimal synchronisation procedures. The signal to noise ratio is not ideal under these circumstances.

In brief, the cell cycles through stages in order to divide and such cycling is in itself due to the cycling of certain proteins, the most renown ones are called precisely "cyclins", which are protein markers of cells division. Cyclin D, E, A, B prevail differently at different stages of the cell cycle as a result of the balanced equation of mRNA transcription and post-transcriptional protein modifications (phosphorylation events mark them for degradation for example). Overall an intertwined and well-coordinated process.

*** EDIT

For a suitable selection of some basic bibliography on the subject, robust sources covering the subject with rigour (less specific and dense than the journal articles I comment bellow) please refer to the following links:

• Molecular Biology of the Cell
• Molecular Cell Biology
• Cell Cycle Regulation
• The Cell Cycle Principles of Control

& even a review of the latter here.

HTH