Evidence in humans supports a role for WRAP53 in the function of and cellular trafficking of the survival of motor neuron (SMN) complex; mutations affecting the SMN complex are responsible for several forms of spinal muscular atrophy (see the human disease model report 'spinal muscular atrophy, SMN-related' FBhh0000352). WRAP53, also known as WDR79, encodes an RNA-binding protein that is a component of the telomerase holoenzyme complex, a ribonucleoprotein complex required for telomere synthesis. The WRAP53 protein is also essential for the formation of nuclear organelles called Cajal bodies; it is involved in cellular trafficking to Cajal bodies of the SMN complex, the telomerase enzyme, and small Cajal body-specific RNAs. There is a single orthologous gene in Drosophila, Dmel\WDR79, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human WRAP53 gene has not been introduced into flies.
Cells of animals homozygous for a loss-of-function allele of Dmel\WDR79 lack Cajal bodies; larvae and adults exhibit locomotor defects. Genetic interactions between Dmel\WDR79 and Dmel\Smn have been reported. Physical interactions with small Cajal-body-specific RNAs (scaRNAs) have been described; see below and in the Dmel\WDR79 gene report.
WRAP53 is also implicated in a form of dyskeratosis congenita (MIM:613988), which appears to be related to its telomerase function. Since Drosophila species maintain telomeres by a different mechanism (see https://www.ncbi.nlm.nih.gov/books/NBK6617/), experiments using Dmel\WDR79 do not address the telomerase component of WRAP53 function or dyskeratosis congenita pathology.
[updated Jul. 2018 by FlyBase; FBrf0222196]
Cajal bodies are a class of nuclear body enriched in small nuclear ribonucleoproteins. Cajal bodies contain a marker protein of unknown function, COIL (coilin), and many components involved in transcription and processing of nuclear RNAs.
WRAP53 (also known as WDR79) encodes an essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex required for telomere synthesis. The WRAP53 mRNA also functions as a p53 antisense transcript that regulates endogenous p53 mRNA levels. [Gene Cards, WRAP53; 2018.07.18]
WRAP53 gene encodes a protein essential for Cajal body formation and involved in cellular trafficking of the survival of motor neuron complex, the telomerase enzyme and small Cajal body-specific RNAs to Cajal bodies. (Mahmoudi et al., 2011; pubmed:21368886).
Survival Motor Neuron protein (SMN), is an evolutionarily conserved protein required for proper locomotion behavior. Both mammalian and Drosophila SMN proteins accumulate in the Cajal bodies (CBs), and cells from spinal muscular atrophy patients are defective in CB structure and abundance. In humans, SMN recruitment to the CB is dependent on its interaction with WRAP53/WDR79/TCAB1. (FBrf0236151 and references cited therein)
One to one: 1 human to 1 fly.
High-scoring ortholog of human WRAP53 (1 Drosophila to 1 human). Dmel\WDR79 shares 35% identity and 50% similarity with the human gene.
