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Prp24 (precursor RNA processing, gene 24) is a protein part of the
pre-messenger RNA A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs ...
splicing process and aids the binding of
U6 snRNA U6 snRNA is the non-coding small nuclear RNA (snRNA) component of U6 snRNP (''small nuclear ribonucleoprotein''), an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, a ...
to
U4 snRNA U4, U-4, or U04 may refer to: Science and technology * U4 spliceosomal RNA, a non-coding RNA component of the major U2-dependent spliceosome * Haplogroup U4 (mtDNA), a human genetic group * U4, unitary group of degree 4 * U-47700, a synthetic opio ...
during the formation of
spliceosome A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs ( snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to sp ...
s. Found in
eukaryotes The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...
from
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...
to ''
E. coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...
'',
fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
, and humans, Prp24 was initially discovered to be an important element of RNA splicing in 1989.
Mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
in Prp24 were later discovered in 1991 to suppress
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
s in U4 that resulted in cold-sensitive strains of yeast, indicating its involvement in the reformation of the U4/U6 duplex after the catalytic steps of splicing.


Biological Role

The process of spliceosome formation involves the U4 and U6
snRNP snRNPs (pronounced "snurps"), or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre- ...
s associating and forming a di-snRNP in the
cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...
. This di-snRNP then recruits another member ( U5) to become a tri-snRNP. U6 must then dissociate from U4 to bond with U2 and become catalytically active. Once splicing has been done, U6 must dissociate from the spliceosome and bond back with U4 to restart the cycle. Prp24 has been shown to promote the binding of U4 and U6 snRNPs. Removing Prp24 results in the accumulation of free U4 and U6, and the subsequent addition of Prp24 regenerates U4/U6 and reduces the amount of free U4 and U6. Naked U6 snRNA is very compact and has little room to form
base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
s with other RNA. However, when U6 snRNP associates with proteins such as Prp24, the structure is much more open, thus facilitating the binding to U4. Prp24 is not present in the U6/U4 duplex itself, and it has been suggested that Prp24 must leave the complex in order for proper base pairs to be formed. It has also been suggested that Prp24 may play a role in destabilizing U4/U6 in order for U6 to pair bases with U2.


Structure

Prp24 has a
molecular weight A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
of 50
kDa The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...
and has been shown to contain four RNA recognition motifs (RRMs) and a conserved 12-amino acid sequence at the
C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...
. RRMs 1 and 2 have been shown to be important for high-
affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...
binding of U6, while RRMs 3 and 4 bind at lower affinity sites on U6. The first three RRMs interact extensively with each other and contain canonical folds that contain a four-stranded
beta-sheet The beta sheet (β-sheet, also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...
and two
alpha-helices An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
. The electropositive surface of RRMs 1 and 2 is a RNA annealing domain while the cleft between RRMs 1 and 2 including the beta-sheet face of RRM2 is a sequence-specific RNA binding site. The C-terminal motif is required for association with
LSm LSM may refer to: Science *Laboratoire Souterrain de Modane (Modane Underground Laboratory), a particle physics laboratory in France *Lanthanum strontium manganite, a crystal used as a cathode material *Confocal microscopy, Laser scanning microsc ...
proteins and contributes to
substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...
(U6) binding and not the catalytic rate of splicing.


Interactions

Prp24 interacts with the U6 snRNA via its RRMs. It has been shown through
chemical modification Chemical modification refers to a number of various processes involving the alteration of the chemical constitution or structure of molecules. Chemical modification of proteins Chemical modification is the change of biomolecular structure and ...
testing that
nucleotides 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 ...
39–57 of U6 (40–43 in particular) are involved in binding Prp24. The LSm proteins are in a consistent configuration on the U6 RNA. It has been proposed that the LSm proteins and Prp24 interact both physically and functionally and the C-terminal motif of Prp24 is important for this interaction. The binding of Prp24 to U6 is enhanced by the binding of Lsm proteins to U6, as is binding of U4 and U6. It was revealed by
electron microscopy An electron microscope is a microscope that uses a beam of electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing i ...
that Prp24 may interact with the LSm protein ring at LSm2.


Homologs

Prp24 has a human
homolog In biology, homology is similarity in anatomical structures or genes between organisms of different taxa due to shared ancestry, ''regardless'' of current functional differences. Evolutionary biology explains homologous structures as retained her ...
,
SART3 Squamous cell carcinoma antigen recognized by T-cells 3 is a protein that in humans is encoded by the ''SART3'' gene. The protein encoded by this gene is an RNA-binding nuclear protein that is a tumor-rejection antigen. This antigen possesses tum ...
. SART3 is a tumor rejection
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
(SART3 stands for "squamous cell carcinoma antigen recognized by T cells, gene 3). The RRMs 1 and 2 in yeast are similar to RRMs in human SART3. The C-terminal domain is also highly conserved from yeast to humans. This protein, like Prp24, interacts with the LSm proteins for the recycling of U6 into the U4/U6 snRNP. It has been proposed that SART3 target U6 to a
Cajal body Cajal bodies (CBs), also coiled bodies, are spherical nuclear bodies of 0.3–1.0 μm in diameter found in the nucleus of proliferative cells like embryonic cells and tumor cells, or metabolically active cells like neurons. CBs are membra ...
or a nuclear inclusion as the site of assembly of the U4/U6 snRNP. SART3 is located on
chromosome 12 Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...
, and a
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...
is likely the cause of
disseminated superficial actinic porokeratosis Disseminated superficial actinic porokeratosis (DSAP) is a non-contagious skin condition with apparent Genetics, genetic origin in the SART3 gene. It most often presents in sun-exposed areas of the body. Some DSAP cases have been reported in patie ...
.


References

{{Reflist, 2


External links


Biological Sciences at Lancaster University
Explanation of pre-mRNA splicing Gene expression Molecular genetics Spliceosome