Abstract
Iron is an essential nutrient critical for many cellular functions including DNA synthesis, ATP generation, and cellular proliferation. Though essential, excessive iron may contribute to the generation of free radicals capable of damaging cellular lipids, proteins, and nucleic acids. As such, the maintenance and control of cellular iron homeostasis is critical to prevent either iron deficiency or iron toxicity conditions. The maintenance of cellular iron homeostasis is largely coordinated by a family of cytosolic RNA binding proteins known as Iron Regulatory Proteins (IRP) that function to post-transcriptionally control the translation and/or stability of mRNA encoding proteins required for iron uptake, storage, transport, and utilization. More recently, a class of small non-coding RNA known as microRNA (miRNA) has also been implicated in the control of iron metabolism. To date, miRNA have been demonstrated to post-transcriptionally regulate the expression of genes associated with iron acquisition (transferrin receptor and divalent metal transporter), iron export (ferroportin), iron storage (ferritin), iron utilization (ISCU), and coordination of systemic iron homeostasis (HFE and hemojevelin). Given the diversity of miRNA and number of potential mRNA targets, characterizing factors that contribute to alterations in miRNA expression, biogenesis, and processing will enhance our understanding of mechanisms by which cells respond to changes in iron demand and/or iron availability to control cellular iron homeostasis.
Highlights
IntroductionAn essential nutrient, is one of the most abundant minerals in the earth’s crust, yet iron deficiency (ID) remains the most common micronutrient deficiency in the world, affecting some
Iron, an essential nutrient, is one of the most abundant minerals in the earth’s crust, yet iron deficiency (ID) remains the most common micronutrient deficiency in the world, affecting some1.6 billion people or nearly 25% of the earth’s population [1]
Whereas hepcidin is considered to be the primary means of regulating systemic iron homeostasis, a family of cytosolic RNA binding proteins known as Iron Regulatory Proteins (IRP) is considered to be the global regulators of cellular iron homeostasis
Summary
An essential nutrient, is one of the most abundant minerals in the earth’s crust, yet iron deficiency (ID) remains the most common micronutrient deficiency in the world, affecting some. Current evidence suggests that miRNA may be key regulators in many facets of human iron homeostasis. To date (April 2013), 21264 precursor miRNA expressing 25141 mature miRNA have been annotated in 193 species and logged in the latest. There are currently 1600 annotated human precursor miRNA expressing 2042 mature miRNA. With thousands of miRNA in numerous species being identified in a relatively short period of time, it was essential to establish criteria to be used in annotating each newly discovered miRNA [11,12]. Designate distinct precursor sequences and genomic loci that express 100% identical mature miRNA [12]. When available sequencing data is not sufficient to designate the predominant strand, a naming convention that identifies the miRNA strand location on the 5′- or 3′-arm of the precursor miRNA is used (e.g., hsa-miR-6725-5p and hsa-miR-6725-3p) [13]
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