molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

, HOTTIP (HOXA transcript at the distal tip) is a

long non-coding RNA Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as mic ...

. The gene encoding HOTTIP is located at the

5′ Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. In a single strand of DNA or RNA, the chemical convention of naming carbon atoms in the nucleotide pentose-sugar-ri ...

tip of the HOXA locus, and coordinates the

activation Activation, in chemistry and biology, is the process whereby something is prepared or excited for a subsequent reaction. Chemistry In chemistry, "activation" refers to the reversible transition of a molecule into a nearly identical chemical or ...

of several of the 5′ HOXA genes. The non-coding RNA is brought into close proximity with the HOXA genes by

chromosomal A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

looping. HOTTIP binds to the

WDR5 WD repeat-containing protein 5 is a protein that in humans is encoded by the ''WDR5'' gene. This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed ...

protein, which forms a complex with the

histone methyltransferase Histone methyltransferases (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of ...

protein MLL. This targets the WDR5-MLL complex to the HOXA region and results in H3K4 methylation and transcriptional activation of the HOXA locus. More recently, HOTTIP has been shown to play a role in Hepatocellular Carcinoma (HCC) progression. HOTTIP expression levels predict metastasis formation and poor disease outcome in HCC patients. HOTTIP has been shown to be transcriptionally regulated by a transcriptional coactivator PSIP1/p52

See also

References

Further reading