The miR-29 microRNA precursor, or pre-miRNA, is a small

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

molecule in the shape of a

stem-loop Stem-loops are nucleic acid Biomolecular structure, secondary structural elements which form via intramolecular base pairing in single-stranded DNA or RNA. They are also referred to as hairpins or hairpin loops. A stem-loop occurs when two regi ...

hairpin A hairpin or hair pin is a long device used to hold a person's hair in place. It may be used simply to secure long hair out of the way for convenience or as part of an elaborate hairstyle or coiffure. The earliest evidence for dressing the ha ...

. Each arm of the hairpin can be processed into one member of a closely related family of short

non-coding RNA A non-coding RNA (ncRNA) is a functional RNA molecule that is not Translation (genetics), translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally imp ...

s that are involved in regulating

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

. The processed, or "mature" products of the precursor molecule are known as microRNA (miRNA), and have been predicted or confirmed in a wide range of species
see 'MIPF0000009' in miRBase: the microRNA database
.

miRNA processing

Animal miRNAs are first transcribed as a primary miRNA molecule. This "pri-miRNA" may contain one or more precursor hairpins, which are freed from the pri-miRNA by the nuclear enzyme

Drosha Drosha is a Class 2 ribonuclease III enzyme that in humans is encoded by the ''DROSHA'' (formerly ''RNASEN'') gene. It is the primary nuclease that executes the initiation step of miRNA processing in the nucleus. It works closely with DGCR8 and ...

. The approximately 70

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

precursor hairpin is exported from the nucleus and subsequently processed by the

Dicer Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into shor ...

enzyme to give a mature miRNA that is on average 22 nucleotides long. Either arm of the precursor may yield a mature RNA, although either the 3' (3p) or the 5' (5p) arm is preferentially processed and loaded into the

RNA-induced silencing complex The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) ...

(RISC) in most cases. For the miR-29 precursor, the 3' arm of the precursor RNA yields the overwhelmingly predominant product (miR-29 or miR-29-3p), although the 5' arm (miR-29* or miR-29-5p) has also been experimentally verified.

The miR-29 family

Many mammalian genomes encode four closely related miR-29 precursors that are transcribed in two transcriptional units. For example, human miR-29a and miR-29b-1 are processed from an

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...

of a long non-coding transcript pri-miRNA (lnc-pri-miRNA) LOC646329 from chromosome 7. miR-29b-2 (identical in sequence to miR-29b-1) and miR-29c are co-transcribed from chromosome 1. The three main mature miRNAs processed from these precursors are known as hsa-miR-29a, hsa-miR-29b, and hsa-miR-29c. Survival analysis across three independent datasets shows that hsa-miR-29c is associated with survival in breast cancer.

Targets of miR-29

The mature products are thought to exert regulatory roles by binding with partial complementarity to microRNA recognition elements (MREs) in the 3' untranslated region (3' UTR) of target transcripts. Experimental evidence suggests that putative targets of mature miR-29 products include the following: *The myeloid leukemia cell differentiation protein (MCL1), an anti-

apoptotic Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes ( morphology) and death. These ...

member of the

Bcl-2 Bcl-2, encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first a ...

family of proteins. *The

TCL1A T-cell leukemia/lymphoma protein 1A is a protein that in humans is encoded by the ''TCL1A'' gene. Interactions TCL1A has been shown to interact with AKT1 RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans i ...

(T cell leukemia/lymphoma 1)

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

, found to be disrupted in many T-cell

leukemias Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' le ...

, but also dysregulated B cell malignancies. *

DNA methyltransferase In biochemistry, the DNA methyltransferase (DNA MTase, DNMT) family of enzymes catalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl ...

DNMT3A DNA (cytosine-5)-methyltransferase 3A (DNMT3A) is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the ''DNMT3A'' gene. This enzyme is ...

and

DNMT3B DNA (cytosine-5)-methyltransferase 3 beta, is an enzyme that in humans in encoded by the DNMT3B gene. Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome. Function CpG methylation ...

, which are frequently upregulated in

lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...

. * Zinc finger protein 36 homolog (ZFP36), also known as tristetraprolin (TTP), an anti-inflammatory and anti-cancer gene. *tumor necrosis factor receptor-associated factor 4 (TRAF4) was identified as miR-29 target in B cells, and as a regulator of CD40 signalling Recently, in an attempt to identify targets at global level using

Quantitative proteomics Quantitative proteomics is an analytical chemistry technique for determining the amount of proteins in a sample. The methods for protein identification are identical to those used in general (i.e. qualitative) proteomics, but include quantificatio ...

SILAC Stable isotope labeling by/with amino acids in cell culture (SILAC) is a technique based on mass spectrometry that detects differences in protein abundance among samples using non-radioactive isotopic labeling. It is a popular method for quantitat ...

approach,

VDAC1 Voltage-dependent anion-selective channel 1 (VDAC-1) is a beta barrel protein that in humans is encoded by the ''VDAC1'' gene located on chromosome 5. It forms an ion channel in the outer mitochondrial membrane (OMM) and also the outer cell membra ...

and

VDAC2 Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the ''VDAC2'' gene on chromosome 10. This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoform ...

were identified as targets of miR-29a in HEK293T cells.

References

External links

*
MIPF0000009
{{miRNA precursor families MicroRNA