Survival of motor neuron or survival motor neuron (SMN) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''
SMN1
Survival of motor neuron 1 (''SMN1''), also known as component of gems 1 or ''GEMIN1'', is a gene that encodes the SMN protein in humans.
Gene
''SMN1'' is the telomeric copy of the gene encoding the SMN protein; the centromeric copy is term ...
'' and ''
SMN2
Survival of motor neuron 2 (''SMN2'') is a gene that encodes the SMN protein (full and truncated) in humans.
Gene
The ''SMN2'' gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four ge ...
''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
s.
SMN is found in the cytoplasm of all animal cells and also in the
nuclear
Nuclear may refer to:
Physics
Relating to the nucleus of the atom:
* Nuclear engineering
*Nuclear physics
*Nuclear power
*Nuclear reactor
*Nuclear weapon
*Nuclear medicine
*Radiation therapy
*Nuclear warfare
Mathematics
*Nuclear space
*Nuclear ...
gems
Gems, or gemstones, are polished, cut stones or minerals.
Gems or GEMS may also refer to:
Arts, entertainment and media
* ''Gems'' (Aerosmith album), 1988
* ''Gems'' (Patti LaBelle album), 1994
* ''Gems'' (Michael Bolton album), 2011
* Gems TV, ...
. It functions in
transcriptional regulation
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from al ...
,
telomerase
Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most euka ...
regeneration and
cellular trafficking. SMN deficiency, primarily due to
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 replication, DNA or viral repl ...
s in ''SMN1'', results in widespread
splicing defects, especially in spinal
motor neurons, and is one cause of
spinal muscular atrophy. Research also showed a possible role of SMN in
neuronal migration
The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The fiel ...
and/or
differentiation.
Function
The SMN protein contains
GEMIN2-binding,
Tudor and YG-Box domains.
It localizes to both the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
and the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
* Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucl ...
. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small
ribonucleoprotein
Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.
Structures
Nucleoproteins tend to be positively charged, facilitating int ...
s (snRNPs). This protein forms heteromeric complexes with proteins such as GEMIN2 and
GEMIN4
Gem-associated protein 4 is a protein that in humans is encoded by the ''GEMIN4'' gene.
Function
The product of this gene is part of the SMN protein complex localized to the cytoplasm, nucleoli, and to discrete nuclear bodies called Gemini b ...
, and also interacts with several proteins known to be involved in the
biogenesis
Spontaneous generation is a superseded scientific theory that held that living creatures could arise from nonliving matter and that such processes were commonplace and regular. It was hypothesized that certain forms, such as fleas, could arise ...
of
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, such as hnRNP U protein and the small nucleolar RNA binding protein.
SMN complex
''SMN complex'' refers to the entire multi-protein complex involved in the assembly of
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, the essential components of
spliceosomal machinery.
The complex, apart from the "proper" survival of motor neuron protein, includes at least six other proteins (
gem-associated protein 2,
3,
4,
5,
6 and
7.
Interactions
SMN has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
Bcl-2
Bcl-2 (B-cell lymphoma 2), encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosi ...
,
*
Coilin
Coilin is a protein that in humans is encoded by the ''COIL'' gene. Coilin got its name from the coiled shape of the Cajal bodies in which it is found. It was first identified using human autoimmune serum.
Function
Coilin protein is one of the ...
,
*
DDX20
Probable ATP-dependent RNA helicase DDX20, also known as DEAD-box helicase 20 and gem-associated protein 3 (GEMIN3), is an enzyme that in humans is encoded by the ''DDX20'' gene.
Function
DEAD box proteins, characterized by the conserved motif ...
,
* DHX9
ATP-dependent RNA helicase A (RHA; also known as DHX9, LKP, and NDHI) is an enzyme that in humans is encoded by the ''DHX9'' gene.
Function
DEAD/DEAH box helicases are proteins, and are putative RNA helicases. They are implicated in a number o ...
,
* FBL,
* FUBP1
Far upstream element-binding protein 1 is a protein that in humans is encoded by the ''FUBP1'' gene.
This gene encodes a ssDNA binding protein that activates the far upstream element (FUSE) of c-myc and stimulates expression of c-myc in undiffere ...
,
* GAR1,[
* GEMIN2,]
* GEMIN4
Gem-associated protein 4 is a protein that in humans is encoded by the ''GEMIN4'' gene.
Function
The product of this gene is part of the SMN protein complex localized to the cytoplasm, nucleoli, and to discrete nuclear bodies called Gemini b ...
,
* GEMIN5,
* GEMIN7,
* HNRNPR
Heterogeneous nuclear ribonucleoprotein R is a protein that in humans is encoded by the ''HNRNPR'' gene.
Function
This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are R ...
,
* KPNB1
Importin subunit beta-1 is a protein that in humans is encoded by the ''KPNB1'' gene.
Function
Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. ...
,
* P53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
,
* SNRPD1, and
* SNRPD2.[
]
Evolutionary conservation
SMN is evolutionarily conserved including the Fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
kingdom, though only fungal organisms with a great number of introns have the ''Smn'' gene (or the splicing factor spf30 paralogue
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...
). Surprisingly, these are filamentous fungus which have mycelia
Mycelium (plural mycelia) is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae. Fungal colonies composed of mycelium are found in and on soil and many other substrates. A typical single spore germinates ...
, so suggesting analogy to the neuronal axons.
See also
* Gideon Dreyfuss
Gideon Dreyfuss is an American biochemist, the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine, and an investigator of the Howard Hughes Medical Institute. He was elected to the Nation ...
References
External links
*
{{Nucleus
Motor system
Spinal muscular atrophy