nap, napts, no-action-potential, male lethal, no action potential
DEAH-box subfamily ATP-dependent helicase - Mle plays an early role in dosage compensations, perhaps in packaging RNA into growing dosage compensation protein complexes - remodels the roX lncRNAs, enabling the long noncoding RNA-mediated assembly of the dosage compensation complex
Gene model reviewed during 5.47
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.48
None of the polypeptides share 100% sequence identity.
1293, 226 (aa); 140 (kD observed); 144 (kD predicted)
Interacts with Top2.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\mle using the Feature Mapper tool.
mle protein is detected in nuclear extracts from adult males and females.
GBrowse - Visual display of RNA-Seq signalsView Dmel\mle in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for identity of: mle CG11680
"mle" alleles fail to complement the paralysis caused by "nap" alleles, indicating that "nap" and "mle" are allelic.
Molecular analysis demonstrated that "mle" mutants are allelic to "nap" mutants.
The mle protein interacts with the most prominent transcriptionally active regions of chromosomes independently of other MSL proteins.
Gene products of the male specific lethal (msl) group of genes including msl-1, msl-2, msl-3, mle, and mof are associated with all female chromosomes at a low level but are sequestered to the X chromosome in males. There is evidence for the presence of nucleation sites for association of msl proteins with the X chromosome rather than individual gene binding sites.
Gene products of the male specific lethal (msl) group of genes preferentially associate with the male X chromosome and may have a role in dosage compensation. This may be achieved by regulating an inverse dosage effect, which would be maintained on the male X and nullified on the autosomes.
Used as a 'bait' in the yeast two-hybrid system to screen for interactors from an imaginal disc cDNA library: Dbp80 is identified.
mof colocalises with the MSL complex on the X chromosome: a sequence of binding events results in the formation of the MSL complex on the X chromosome in males and in the targeting of mof to its presumed site of action. mle is necessary but only as a structural component for the recruitment of mof to the X chromosome.
In the germline mle is not involved in chromosomal dosage compensation but may be involved in post-transcriptional gene regulation. Loss of mle has no detectable effect on expression or localisation of acetylated His4.
X chromosome proteins associated with dosage compensation in melanogaster are sufficiently conserved to allow significant antibody cross-reaction to D.simulans, D.virilis, D.americana.americana and D.pseudoobscura.pseudoobscura chromosomes. Cross reaction is also observed in the X chromosome and the X2 chromosome (2 copies in females and 1 in males) of D.miranda. These results provide evidence that the male-specific lethal proteins can be acquired on previously unrelated chromosome arms during evolution.
Male-specific lethal (MSL) proteins accumulate in a subregion of male nuclei (the X chromosome) beginning at late blastoderm stage. X chromosomal binding of the MSLs is observed throughout embryonic and larval development in both diploid and polytene tissues. His4 colocalises with the MSLs in embryos. Binding of the MSLs is interdependent in diploid cells and is prevented in female embryonic cells by Sxl.
Association of mle with the polytene X chromosome is RNase sensitive and mutations in the ATPase motifs affect mle function. The carboxyl terminus of mle may have a potential role in general affinity to RNA.
The products of msl-1, msl-2, mle and msl-3 loci specifically associate with hundreds of sites along the X chromosome in males, but not in females. The binding of each of the four proteins requires the functional products from the other three. 2X3A individuals are mosaic for both Sxl expression and msl-1, msl-2, mle and msl-3 binding to the X chromosome, with a perfect inverse correlation at the cellular level between Sxl expression and msl-1, msl-2, mle and msl-3 X chromosome binding.
Heartbeat of mlenap-ts1 individuals is seriously impaired, becoming arrhythmic at elevated temperatures.
Immunostaining of embryonic and larval stages demonstrates that His4, msl-1 and msl-3 are associated with the male X chromosome as early as gastrulation, while mle binding is not detected until the late embryonic/late larval stages.
Elements needed for dosage compensation are localised to the X chromosome only after blastoderm and msl-dependent dosage compensation is not necessary during the first part of embryogenesis. This suggest the existance of an additional msl-independent dosage compensation mechanism; dosage compensation of run expression at blastoderm is not dependent on male specific lethal genes.
The gene products of mle, msl-1 bind to the male X chromosome in an identical pattern, and the binding sites of H4Ac16 acetylated form of the His4 product are largely coincident with the mle/msl-1 binding sites. Association of H4Ac16 protein with the male X chromosome requires wild type function of msl-1, msl-2, mle and msl-3.
The four msl gene products interact to form a multiprotein complex.
Antisera to mle protein label the euchromatic X chromosome through mitosis, but neither the X heterochromatin nor autosomes.
mle was identified by two very different mutant phenotypes, male-lethality ('mle') and rapid paralysis of larvae or adults when exposed to 37oC ('napts').
The 'mle' group phenotype: Mutants are defective for dosage compensation in males. Homozygous males die, but homozygous females survive. Males produced by homozygous females die during the third larval instar, whereas those produced by heterozygous females are late pupal lethals. Females transformed into phenotypic males (tra1) or intersexes (dsx1) unaffected by mle1, i.e. mle acts only upon single-X-bearing flies. mle4 males surviving at 18oC are sterile, small and slow developing. Polytene X chromosome of mle1 males appears narrower and more densely stained than that of control males. The 'nap' group phenotype: Larvae or adults become rapidly paralyzed when exposed to 37oC and rapidly recover on return to lower temperatures.
Slight reduction in the extent of branching caused by mlenap-ts1 at permissive temperature; the increase in branching (and higher than normal number of varicosities on motor-neurites) induced by an eag Sh double mutant was suppressed by mlenap-ts1 (re. low-temperature rearing).
Action potentials in the giant fiber (GF) pathway of adults are not blocked at temperatures up to 43oC. The long-latency phenotype disappears as the temperature is raised to 35oC.
Experiments involving one-time rearing at low temperature caused mlenap-ts1 to paralyze at relatively low temperatures. Action potentials in the giant fiber (GF) pathway of adults are not blocked at temperatures up to 43oC, though the latency from brain stimulation to response of thoracic muscles are aberrantly long, even at low temperatures. 'Following frequency' of mlenap-ts1 thoracic muscle responses (re. GF pathway stimulation) is reduced at elevated temperatures, an effect which can be reversed by injection of 4-amino-pyridine.
Mutation does not seem to modify the expression of sodium currents in embryonic neurons.
mle1 pole cell transplanted into wild-type hosts are incapable of undergoing normal spermatogenesis.
In mosaic experiments, cuticular clones of parats1 in a mlenap-ts1 background (after low-temperature development) have non-functioning sensory cells, probably due to lack of nerve conduction which, however, did not cause any anatomical abnormalities involving the central projections of these sensory neurons.
Rearing stocks chronically at room temperature or above causes mlenap-ts1 to 'adapt' such that higher temperatures (> 40oC) are required for paralysis. Exposure of mlenap-ts1 males to high temperature causes arrest of oscillator underlying rhythmic component of courtship song.
Brain membrane extracts of mlenap-ts1, assayed at low or high temperatures, have subnormal levels of saxitoxin, though there are no qualitative alterations of this binding activity (kD is normal).
Cultured neurons from mlenap-ts1 larvae are 4 to 5-fold more resistant than wild-type cells to killing effects of veratridine, irrespective of temperature (22oC vs 35oC).
Cultured neurons from mlenap-ts1 larvae are not affected by TTX, their general growth characteristics are normal.
Brain membrane extracts of mlenap-ts1, assayed at low or high temperatures, have subnormal levels of tetrodotoxin.
Few homozygous mle1 gynandromorphs survive; X0 patches small, with small bristles, and mostly confined to abdomen.
Mutants show decreased levels of X-linked-enzyme activities (G6PD, 6GPD, FUM) but not autosomally encoded enzymes (ADH, AO, GPDH, IDH) in homozygous mle4 male larvae when compared with non-msl controls.
The incorporation of labeled uridine by the polytene X chromosome relative to that of 2R is lower than normal in mle4 males.
Axonal conduction (but not synaptic transmission) fails in mutant larvae at high temperatures. At permissive temperatures, refractory period for elicitation of a series of action potentials is abnormally long and mutants are hypersensitive to blocking effects of tetrodotoxin (TTX) on action potentials. mlenap-ts1 is unconditionally lethal in a double mutant with parats1 (death occurring during 1st larval instar).
Axonal conduction (but not synaptic transmission) fails in larvae at high temperatures.