The MIR146A gene provides instructions for making microRNA-146a (miR-146a). MicroRNAs (miRNAs) are short lengths of RNA, a chemical cousin of DNA. These molecules control gene expression by blocking the process of protein production. MiR-146a is abundant in immature blood cells and controls the expression of hundreds of genes. This microRNA is thought to be involved in normal blood cell development. In particular, miR-146a appears to play a role in the growth and division of blood cells called megakaryocytes, which produce platelets, the cells involved in blood clotting.
The MIR146A gene is involved in a condition called 5q minus (5q-) syndrome. This condition is a type of bone marrow disorder called myelodysplastic syndrome (MDS), in which immature blood cells fail to develop normally. Individuals with 5q- syndrome often have a shortage of red blood cells (anemia) and abnormalities in megakaryocytes. Affected individuals also have an increased risk of developing a fast-growing blood cancer known as acute myeloid leukemia (AML).
5q- syndrome is caused by deletion of a region of DNA from the long (q) arm of chromosome 5. This deletion occurs in immature blood cells during a person's lifetime and affects one copy of chromosome 5 in each cell. Most people with 5q- syndrome are missing a sequence of about 1.5 million DNA building blocks (base pairs), also written as 1.5 megabases (Mb). This deleted region contains 40 genes, often including MIR146A. Loss of one copy of the MIR146A gene reduces the amount of the microRNA miR-146a in cells. As a result, levels of proteins whose production is normally blocked by miR-146a are elevated, which leads to the abnormal development of megakaryocytes that occurs in 5q- syndrome. Research suggests that the other features of the condition are associated with other genes in the deleted segment of DNA.