PRPF31

Last updated
PRPF31
Protein PRPF31 PDB 2ozb.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PRPF31 , pre-mRNA processing factor 31, NY-BR-99, PRP31, RP11, SNRNP61
External IDs OMIM: 606419 MGI: 1916238 HomoloGene: 5980 GeneCards: PRPF31
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_015629

NM_001159714
NM_027328

RefSeq (protein)

NP_056444
NP_056444.3

NP_001153186
NP_081604

Location (UCSC) Chr 19: 54.12 – 54.13 Mb Chr 7: 3.63 – 3.65 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae), also known as PRPF31, is a protein which in humans is encoded by the PRPF31 gene. [5]

Contents

Function

PRPF31 is the gene coding for the splicing factor hPRP31. It is essential for the formation of the spliceosome hPRP31 is associated with the U4/U6 di-snRNP and interacts with another splicing factor, hPRP6, to form the U4/U6-U5 tri-snRNP. It has been shown that when hPRP31 is knocked down by RNAi, U4/U6 di-snRNPs accumulate in the Cajal bodies and the U4/U6-U5 tri-snRNP cannot form. [6]

PRPF31 is recruited to introns following the attachment of U4 and U6 RNAs and the 15.5K protein NHP2L1. The addition of PRPF31 is crucial for the transition of the spliceosomal complex to the activated state. [7]

Clinical significance

A mutation in PRPF31 is one of 4 known mutations in splicing factors which are known to cause retinitis pigmentosa. The first mutation in PRPF31 was discovered by Vithana et al. in 2001. [5] Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by a progressive degeneration of photoreceptors, eventually resulting in severe visual impairment. [8]

Inheritance

Mutations in PRPF31 are inherited in an autosomal dominant manner, accounting for 2.5% of cases of autosomal dominant retinitis pigmentosa (adRP) in a mixed UK population. [9] However, the inheritance pattern of PRPF31 mutations is atypical of dominant inheritance, showing the phenomenon of partial penetrance, whereby a dominant mutations appear to "skip" generations. This is thought to be due to the presence of two wild type alleles, a high-expressivity allele and a low-expressivity allele. If a patient has a mutant allele and a high-expressivity allele, they do not show disease phenotype. If a patient has a mutant allele and a low-expressivity allele, the residual level of protein falls beneath the threshold for normal function, and so they do show disease phenotype. The inheritance pattern of PRPF31 can therefore be thought of as a variation of haploinsufficiency. This variant of haploinsufficiency is only seen in two other human diseases: Erythropoietic protoporphyria, caused by mutations in the FECH gene; and hereditary elliptocytosis, caused by mutations in the spectrin gene. [10] [11]

Related Research Articles

<span class="mw-page-title-main">Retinitis pigmentosa</span> Gradual retinal degeneration leading to progressive sight loss

Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision. As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.

<span class="mw-page-title-main">Haploinsufficiency</span> Concept in genetics

Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type phenotype. Haploinsufficiency may arise from a de novo or inherited loss-of-function mutation in the variant allele, such that it yields little or no gene product. Although the other, standard allele still produces the standard amount of product, the total product is insufficient to produce the standard phenotype. This heterozygous genotype may result in a non- or sub-standard, deleterious, and (or) disease phenotype. Haploinsufficiency is the standard explanation for dominant deleterious alleles.

<span class="mw-page-title-main">PRPF8</span> Protein-coding gene in the species Homo sapiens

Pre-mRNA-processing-splicing factor 8 is a protein that in humans is encoded by the PRPF8 gene.

<span class="mw-page-title-main">Retinitis pigmentosa GTPase regulator</span> Protein-coding gene in the species Homo sapiens

X-linked retinitis pigmentosa GTPase regulator is a GTPase-binding protein that in humans is encoded by the RPGR gene. The gene is located on the X-chromosome and is commonly associated with X-linked retinitis pigmentosa (XLRP). In photoreceptor cells, RPGR is localized in the connecting cilium which connects the protein-synthesizing inner segment to the photosensitive outer segment and is involved in the modulation of cargo trafficked between the two segments.

<span class="mw-page-title-main">Peripherin 2</span> Protein-coding gene in the species Homo sapiens

Peripherin-2 is a protein, that in humans is encoded by the PRPH2 gene. Peripherin-2 is found in the rod and cone cells of the retina of the eye. Defects in this protein result in one form of retinitis pigmentosa, an incurable blindness.

<span class="mw-page-title-main">U2 small nuclear RNA auxiliary factor 1</span> Protein-coding gene in the species Homo sapiens

Splicing factor U2AF 35 kDa subunit is a protein that in humans is encoded by the U2AF1 gene.

<span class="mw-page-title-main">SF3A1</span> Protein-coding gene in the species Homo sapiens

Splicing factor 3 subunit 1 is a protein that in humans is encoded by the SF3A1 gene.

<span class="mw-page-title-main">PRPF3</span> Protein-coding gene in the species Homo sapiens

U4/U6 small nuclear ribonucleoprotein Prp3 is a protein that in humans is encoded by the PRPF3 gene.

<span class="mw-page-title-main">PRPF6</span> Protein-coding gene in the species Homo sapiens

Pre-mRNA-processing factor 6 is a protein that in humans is encoded by the PRPF6 gene.

<span class="mw-page-title-main">PRPF4B</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase PRP4 homolog is an enzyme that in humans is encoded by the PRPF4B gene.

<span class="mw-page-title-main">PRPF4</span> Protein-coding gene in the species Homo sapiens

U4/U6 small nuclear ribonucleoprotein Prp4 is a protein that in humans is encoded by the PRPF4 gene. The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. PRPF4 is 1 of several proteins that associate with U4 and U6 snRNPs.[supplied by OMIM]

<span class="mw-page-title-main">TULP1</span> Protein-coding gene in the species Homo sapiens

Tubby-related protein 1 is a protein that in humans is encoded by the TULP1 gene.

<span class="mw-page-title-main">RP1</span> Protein-coding gene in humans

Oxygen-regulated protein 1 also known as retinitis pigmentosa 1 protein (RP1) is a protein that in humans is encoded by the RP1 gene.

<span class="mw-page-title-main">FSCN2</span> Protein-coding gene in the species Homo sapiens

Fascin-2 is a protein that in humans is encoded by the FSCN2 gene.

<span class="mw-page-title-main">RP9</span> Protein-coding gene in the species Homo sapiens

Retinitis pigmentosa 9 (autosomal dominant), also known as RP9 or PAP-1, is a protein which in humans is encoded by the RP9 gene.

<span class="mw-page-title-main">PPIH</span> Protein-coding gene in the species Homo sapiens

Peptidyl-prolyl cis-trans isomerase H is an enzyme that in humans is encoded by the PPIH gene.

<span class="mw-page-title-main">IMPDH1</span> Protein-coding gene in the species Homo sapiens

Inosine-5'-monophosphate dehydrogenase 1, also known as IMP dehydrogenase 1, is an enzyme that in humans is encoded by the IMPDH1 gene.

<span class="mw-page-title-main">Prp24</span>

Prp24 is a protein part of the pre-messenger RNA splicing process and aids the binding of U6 snRNA to U4 snRNA during the formation of spliceosomes. Found in eukaryotes from yeast to E. coli, fungi, and humans, Prp24 was initially discovered to be an important element of RNA splicing in 1989. Mutations in Prp24 were later discovered in 1991 to suppress mutations 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.

<span class="mw-page-title-main">Retinal degeneration (rhodopsin mutation)</span> Retinopathy

Retinal degeneration is a retinopathy which consists in the deterioration of the retina caused by the progressive death of its cells. There are several reasons for retinal degeneration, including artery or vein occlusion, diabetic retinopathy, R.L.F./R.O.P., or disease. These may present in many different ways such as impaired vision, night blindness, retinal detachment, light sensitivity, tunnel vision, and loss of peripheral vision to total loss of vision. Of the retinal degenerative diseases retinitis pigmentosa (RP) is a very important example.

<span class="mw-page-title-main">Prp8</span>

Prp8 refers to both the Prp8 protein and Prp8 gene. Prp8's name originates from its involvement in pre-mRNA processing. The Prp8 protein is a large, highly conserved, and unique protein that resides in the catalytic core of the spliceosome and has been found to have a central role in molecular rearrangements that occur there. Prp8 protein is a major central component of the catalytic core in the spliceosome, and the spliceosome is responsible for splicing of precursor mRNA that contains introns and exons. Unexpressed introns are removed by the spliceosome complex in order to create a more concise mRNA transcript. Splicing is just one of many different post-transcriptional modifications that mRNA must undergo before translation. Prp8 has also been hypothesized to be a cofactor in RNA catalysis.

References

  1. 1 2 3 ENSG00000105618 GRCh38: Ensembl release 89: ENSG00000275885, ENSG00000105618 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000008373 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 Vithana EN, Abu-Safieh L, Allen MJ, Carey A, Papaioannou M, Chakarova C, Al-Maghtheh M, Ebenezer ND, Willis C, Moore AT, Bird AC, Hunt DM, Bhattacharya SS (August 2001). "A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11)". Mol. Cell. 8 (2): 375–81. doi: 10.1016/S1097-2765(01)00305-7 . PMID   11545739.
  6. Schaffert N, Hossbach M, Heintzmann R, Achsel T, Lührmann R (August 2004). "RNAi knockdown of hPrp31 leads to an accumulation of U4/U6 di-snRNPs in Cajal bodies". EMBO J. 23 (15): 3000–9. doi:10.1038/sj.emboj.7600296. PMC   514917 . PMID   15257298.
  7. Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Lührmann R, Carlomagno T, Wahl MC (April 2007). "Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP". Science. 316 (5821): 115–20. Bibcode:2007Sci...316..115L. doi:10.1126/science.1137924. hdl: 11858/00-001M-0000-0012-E16C-F . PMID   17412961. S2CID   22091845.
  8. "Entrez Gene: PRPF31 PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae)".
  9. Waseem NH, Vaclavik V, Webster A, Jenkins SA, Bird AC, Bhattacharya SS (March 2007). "Mutations in the gene coding for the pre-mRNA splicing factor, PRPF31, in patients with autosomal dominant retinitis pigmentosa". Investigative Ophthalmology & Visual Science. 48 (3): 1330–4. doi:10.1167/iovs.06-0963. PMID   17325180.
  10. Randon J, Boulanger L, Marechal J, Garbarz M, Vallier A, Ribeiro L, Tamagnini G, Dhermy D, Delaunay J (Nov 1994). "A variant of spectrin low-expression allele alpha LELY carrying a hereditary elliptocytosis mutation in codon 28". Br J Haematol. 88 (3): 534–40. doi:10.1111/j.1365-2141.1994.tb05070.x. PMID   7819065. S2CID   39527747.
  11. Gouya L, Puy H, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y, Deybach JC (Jun 1998). "Inheritance in erythropoietic protoporphyria: a common wild-type ferrochelatase allelic variant with low expression accounts for clinical manifestation". Am J Hum Genet. 93 (6): 2150–10. PMID   10068685.

Further reading