Maelstrom gene

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Maelstrom
Identifiers
Organism Drosophila melanogaster
SymbolMael
UniProt Q9VNS0
Search for
Structures Swiss-model
Domains InterPro

The gene Maelstrom, Mael, creates a protein, which was first located in Drosophila melanogaster in the nuage perinuclear structure and has functionality analogous to the spindle, spn, gene class. [1] Its mammalian homolog is MAEL.

Contents

In Drosophila

Maelstrom helps establish anterior-posterior and dorsal-ventral symmetry by coordinating to the Microtubule-Organizing Center (MTOC) [2] and assists Vasa establish a concentration gradient of Bicaudal D (BicD) [1] in the developing Drosophila oocyte. Similar to other spindle-class genes, maelstrom defects can lead to the failed production of a karyosome. [1] Mael has also been shown to repress microRNA-7 (miR-7), which in turn regulates the Bag-of-marbles (BAM) protein and secures correct germline differentiation. [3]

Short RNAs are well-known to silence TEs (transposable elements) through the RNAi (RNA interference) pathway, and Piwi-associated RNAs (piRNAs) play a crucial role in transposon silencing in the germline. The Maelstrom protein forms a complex with piRISC to silence transposons and therefore stabilize the germline cell genome. [4]

In mammals

A knockout model for MAEL, the mammalian homolog of Drosophila’s Maelstrom, was created by homologous recombination in mice to create Mael null mice. In the knockout mice, meiotic chromosome synapsis is defective. In addition, spermatogenesis fails due to sperm DNA damage caused by the derepression of transposable elements. [5]

MAEL has also recently been associated with human cancer. An experiment showed MAEL expression throughout a majority of cancer cell types, including lung cancer, breast cancer, prostate cancer, and colon cancer and in turn suggests MAEL as a constituent of the cancer/testis gene class. [6]

Related Research Articles

<span class="mw-page-title-main">Meiosis</span> Cell division producing haploid gametes

Meiosis is a special type of cell division of germ cells and apicomplexans in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a cell with two copies of each chromosome again, the zygote.

<span class="mw-page-title-main">Transposable element</span> Semiparasitic DNA sequence

A transposable element is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transposition often results in duplication of the same genetic material. In the human genome, L1 and Alu elements are two examples. Barbara McClintock's discovery of them earned her a Nobel Prize in 1983. Its importance in personalized medicine is becoming increasingly relevant, as well as gaining more attention in data analytics given the difficulty of analysis in very high dimensional spaces.

<span class="mw-page-title-main">Centrosome</span> Cell organelle in animal cell helping in cell division

In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progression. The centrosome provides structure for the cell. The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes and therefore use other structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species.

<span class="mw-page-title-main">Dicer</span> Enzyme that cleaves double-stranded RNA (dsRNA) into short dsRNA fragments

Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the DICER1 gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short double-stranded RNA fragments called small interfering RNA and microRNA, respectively. These fragments are approximately 20–25 base pairs long with a two-base overhang on the 3′-end. Dicer facilitates the activation of the RNA-induced silencing complex (RISC), which is essential for RNA interference. RISC has a catalytic component Argonaute, which is an endonuclease capable of degrading messenger RNA (mRNA).

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) fragments, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA), the complex functions as a key tool in gene regulation. The single strand of RNA acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in defense against viral infections, as it is triggered by the presence of double-stranded RNA (dsRNA).

An asymmetric cell division produces two daughter cells with different cellular fates. This is in contrast to symmetric cell divisions which give rise to daughter cells of equivalent fates. Notably, stem cells divide asymmetrically to give rise to two distinct daughter cells: one copy of the original stem cell as well as a second daughter programmed to differentiate into a non-stem cell fate.

Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi-subfamily Argonaute proteins. These piRNA complexes are mostly involved in the epigenetic and post-transcriptional silencing of transposable elements and other spurious or repeat-derived transcripts, but can also be involved in the regulation of other genetic elements in germ line cells.

<span class="mw-page-title-main">Piwi</span> Genes and regulatory proteins

Piwi genes were identified as regulatory proteins responsible for stem cell and germ cell differentiation. Piwi is an abbreviation of P-elementInduced WImpy testis in Drosophila. Piwi proteins are highly conserved RNA-binding proteins and are present in both plants and animals. Piwi proteins belong to the Argonaute/Piwi family and have been classified as nuclear proteins. Studies on Drosophila have also indicated that Piwi proteins have no slicer activity conferred by the presence of the Piwi domain. In addition, Piwi associates with heterochromatin protein 1, an epigenetic modifier, and piRNA-complementary sequences. These are indications of the role Piwi plays in epigenetic regulation. Piwi proteins are also thought to control the biogenesis of piRNA as many Piwi-like proteins contain slicer activity which would allow Piwi proteins to process precursor piRNA into mature piRNA.

RNA silencing or RNA interference refers to a family of gene silencing effects by which gene expression is negatively regulated by non-coding RNAs such as microRNAs. RNA silencing may also be defined as sequence-specific regulation of gene expression triggered by double-stranded RNA (dsRNA). RNA silencing mechanisms are conserved among most eukaryotes. The most common and well-studied example is RNA interference (RNAi), in which endogenously expressed microRNA (miRNA) or exogenously derived small interfering RNA (siRNA) induces the degradation of complementary messenger RNA. Other classes of small RNA have been identified, including piwi-interacting RNA (piRNA) and its subspecies repeat associated small interfering RNA (rasiRNA).

In cell biology, microtubule nucleation is the event that initiates de novo formation of microtubules (MTs). These filaments of the cytoskeleton typically form through polymerization of α- and β-tubulin dimers, the basic building blocks of the microtubule, which initially interact to nucleate a seed from which the filament elongates.

Stem-cell niche refers to a microenvironment, within the specific anatomic location where stem cells are found, which interacts with stem cells to regulate cell fate. The word 'niche' can be in reference to the in vivo or in vitro stem-cell microenvironment. During embryonic development, various niche factors act on embryonic stem cells to alter gene expression, and induce their proliferation or differentiation for the development of the fetus. Within the human body, stem-cell niches maintain adult stem cells in a quiescent state, but after tissue injury, the surrounding micro-environment actively signals to stem cells to promote either self-renewal or differentiation to form new tissues. Several factors are important to regulate stem-cell characteristics within the niche: cell–cell interactions between stem cells, as well as interactions between stem cells and neighbouring differentiated cells, interactions between stem cells and adhesion molecules, extracellular matrix components, the oxygen tension, growth factors, cytokines, and the physicochemical nature of the environment including the pH, ionic strength and metabolites, like ATP, are also important. The stem cells and niche may induce each other during development and reciprocally signal to maintain each other during adulthood.

Period (per) is a gene located on the X chromosome of Drosophila melanogaster. Oscillations in levels of both per transcript and its corresponding protein PER have a period of approximately 24 hours and together play a central role in the molecular mechanism of the Drosophila biological clock driving circadian rhythms in eclosion and locomotor activity. Mutations in the per gene can shorten (perS), lengthen (perL), and even abolish (per0) the period of the circadian rhythm.

<span class="mw-page-title-main">PLK1</span> Mammalian protein found in Homo sapiens

Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the PLK1 gene.

<span class="mw-page-title-main">PRC1</span> Protein-coding gene in the species Homo sapiens

Protein Regulator of cytokinesis 1 (PRC1) is a protein that in humans is encoded by the PRC1 gene and is involved in cytokinesis.

<span class="mw-page-title-main">CKAP5</span> Protein-coding gene in the species Homo sapiens

Cytoskeleton-associated protein 5 is a microtubule-associated protein that in humans is encoded by the CKAP5 gene. It is the homolog of the Xenopus protein XMAP215 and is also known as ch-Tog.

Vasa is an RNA binding protein with an ATP-dependent RNA helicase that is a member of the DEAD box family of proteins. The vasa gene is essential for germ cell development and was first identified in Drosophila melanogaster, but has since been found to be conserved in a variety of vertebrates and invertebrates including humans. The Vasa protein is found primarily in germ cells in embryos and adults, where it is involved in germ cell determination and function, as well as in multipotent stem cells, where its exact function is unknown.

Transposon silencing is a form of transcriptional gene silencing targeting transposons. Transcriptional gene silencing is a product of histone modifications that prevent the transcription of a particular area of DNA. Transcriptional silencing of transposons is crucial to the maintenance of a genome. The “jumping” of transposons generates genomic instability and can cause extremely deleterious mutations. Transposable element insertions have been linked to many diseases including hemophilia, severe combined immunodeficiency, and predisposition to cancer. The silencing of transposons is therefore extremely critical in the germline in order to stop transposon mutations from developing and being passed on to the next generation. Additionally, these epigenetic defenses against transposons can be heritable. Studies in Drosophila, Arabidopsis thaliana, and mice all indicate that small interfering RNAs are responsible for transposon silencing. In animals, these siRNAS and piRNAs are most active in the gonads.

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

Transposable elements are pieces of genetic material that are capable of splicing themselves into a host genome and then self propagating throughout the genome, much like a virus. Retrotransposons are a subset of transposable elements that use an RNA intermediate and reverse transcribe themselves into the genome. Retrotransposon proliferation may lead to insertional mutagenesis, disrupt the process of DNA repair, or cause errors during chromosomal crossover, and so it is advantageous for an organism to possess the means to suppress or "silence" retrotransposon activity.

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

The fusome is a membranous structure found in the developing germ cell cysts of many insect orders. Initial description of the fusome occurred in the 19th century and since then the fusome has been extensively studied in Drosophila melanogaster male and female germline development. This structure has roles in maintaining germline cysts, coordinating the number of mitotic divisions prior to meiosis, and oocyte determination by serving as a structure for intercellular communication.

Barry James Thompson is an Australian and British developmental biologist and cancer biologist. Thompson is known for identifying genes, proteins and mechanisms involved in epithelial polarity, morphogenesis and cell signaling via the Wnt and Hippo signaling pathways, which have key roles in human cancer.

References

  1. 1 2 3 Findley, S. D.; Tamanaha, M.; Clegg, N. J.; Ruohola-Baker, H. (2003). "Maelstrom, a Drosophila spindle-class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage". Development. 130 (5): 859–871. doi:10.1242/dev.00310. PMID   12538514. S2CID   13344310.
  2. Sato, K.; Nishida, K. M.; Shibuya, A.; Siomi, M. C.; Siomi, H. (2011). "Maelstrom coordinates microtubule organization during Drosophila oogenesis through interaction with components of the MTOC". Genes & Development. 25 (22): 2361–2373. doi:10.1101/gad.174110.111. PMC   3222902 . PMID   22085963.
  3. Pek, J. W.; Lim, A. K.; Kai, T. (2009). "Drosophila maelstrom ensures proper germline stem cell lineage differentiation by repressing microRNA-7". Developmental Cell. 17 (3): 417–424. doi: 10.1016/j.devcel.2009.07.017 . PMID   19758565.
  4. Sokolova, O. A.; Yakushev, E. Yu.; Stolyarenko, A. D.; Mikhaleva, E. A.; Gvozdev, V. A.; Klenov, M. S. (2011). "Interplay of transposon-silencing genes in the germline of Drosophila melanogaster". Molecular Biology. 45 (4): 582–590. doi:10.1134/S0026893311030174. S2CID   2574989.
  5. Soper, S. F.; Van Der Heijden, G. W.; Hardiman, T. C.; Goodheart, M.; Martin, S. L.; De Boer, P.; Bortvin, A. (2008). "Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis". Developmental Cell. 15 (2): 285–297. doi:10.1016/j.devcel.2008.05.015. PMC   2546488 . PMID   18694567.
  6. Xiao, L.; Wang, Y.; Zhou, Y.; Sun, Y.; Sun, W.; Wang, L.; Zhou, C.; Zhou, J.; Zhang, J. (2010). "Identification of a novel human cancer/Testis gene MAEL that is regulated by DNA methylation". Molecular Biology Reports. 37 (5): 2355–2360. doi:10.1007/s11033-009-9741-x. PMID   19693694. S2CID   20314903.