Biomedical Engineering Reference
In-Depth Information
Chapter 1
A General Introduction to MicroRNAs,
Their Investigation and Exploitation in
CHO Cell Lines
Lyne Jossé, Lin Zhang and C. Mark Smales
Abstract
MicroRNAs are small (20-23 nucleotides) non-coding RNA molecules
that mainly act as negative regulators of gene expression by binding to target
mRNAs in their 3
UTR. In this chapter, we provide a brief account of the
in silico
and experimental tools available for researchers working in protein engineering
in eukaryotic cell factories. In considering the wide influence of microRNAs,
we place a special emphasis on the cellular effects associated with the manipulation
of microRNA and high yield of protein production with reference to use in Chinese
hamster ovary (CHO) expression systems.
Keywords
MicroRNA
biogenesis
·
MicroRNA
editing
·
MicroRNA
binding
specificity
·
MicroRNA stability
·
MicroRNA abundance
1.1
Introduction
MicroRNAs are central to many cellular processes and can regulate a broad range
of targets. This versatility potentially opens many new windows of opportunity for
the biopharmaceutical industry in terms of controlling gene expression and cell phe-
notype in industrial CHO cell lines, particularly as cell engineering strategies which
target multiple genes are increasingly accepted as the most likely to impact upon
desired phenotypes. To date the majority of studies on these molecules have been
undertaken with respect to cancer therapy and much of this knowledge can be di-
rectly related to industrial phenotypes (e.g. those that control growth). Whilst still a
relatively poorly investigated area of gene regulation, the field has benefited from the
development of deep sequencing and RNA sequencing technologies coupled with
comprehensive database platforms which are regularly updated. In addition to the
characterisation of microRNA dynamics, the current effort to annotate the CHO
genome will most certainly accelerate the progression of microRNA investigations
L. Jossé (
)
C. M. Smales (
)
Centre for Molecular Processing and School of Biosciences, University of Kent,
CT2 7NJ Canterbury, Kent, UK
e-mail: c.m.smales@kent.ac.uk
L. Zhang
Pfizer Inc, 1 Burtt Road, Andover, MA 01810, USA
·
