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LSm
In molecular biology, LSm proteins are a family of RNA-binding proteins found in virtually every cellular organism. LSm is a contraction of 'like Sm', because the first identified members of the LSm protein family were the Sm proteins. LSm proteins are defined by a characteristic three-dimensional structure and their assembly into rings of six or seven individual LSm protein molecules, and play a large number of various roles in mRNA processing and regulation.
The Sm proteins were first discovered as antigens targeted by so-called anti-Sm antibodies in a patient with a form of systemic lupus erythematosus (SLE), a debilitating autoimmune disease. They were named Sm proteins in honor of Stephanie Smith, a patient who suffered from SLE. Other proteins with very similar structures were subsequently discovered and named LSm proteins. New members of the LSm protein family continue to be identified and reported.
Proteins with similar structures are grouped into a hierarchy of protein families, superfamilies, and folds. The LSm protein structure is an example of a small beta sheet folded into a short barrel. Individual LSm proteins assemble into a six or seven member doughnut ring (more properly termed a torus), which usually binds to a small RNA molecule to form a ribonucleoprotein complex. The LSm torus assists the RNA molecule to assume and maintain its proper three-dimensional structure. Depending on which LSm proteins and RNA molecule are involved, this ribonucleoprotein complex facilitates a wide variety of RNA processing including degradation, editing, splicing, and regulation.
Alternate terms for LSm family are LSm fold and Sm-like fold, and alternate capitalization styles such as lsm, LSM, and Lsm are common and equally acceptable.
The story of the discovery of the first LSm proteins begins with a young woman, Stephanie Smith, who was diagnosed in 1959 with systemic lupus erythematosus (SLE), eventually succumbing to complications of the disease in 1969 at the age of 22. During this period, she was treated at New York's Rockefeller University Hospital, under the care of Dr. Henry Kunkel and Dr. Eng Tan. As those with an autoimmune disease, SLE patients produce antibodies to antigens in their cells' nuclei, most frequently to their own DNA. However, Kunkel and Tan found in 1966 that Smith produced antibodies to a set of nuclear proteins, which they named the 'smith antigen' (Sm Ag). About 30% of SLE patients produce antibodies to these proteins, as opposed to double stranded DNA. This discovery improved diagnostic testing for SLE, but the nature and function of this antigen was unknown.
Research continued during the 1970s and early 1980s. The smith antigen was found to be a complex of ribonucleic acid (RNA) molecules and multiple proteins. A set of uridine-rich small nuclear RNA (snRNA) molecules was part of this complex, and given the names U1, U2, U4, U5 and U6. Four of these snRNAs (U1, U2, U4 and U5) were found to be tightly bound to several small proteins, which were named SmB, SmD, SmE, SmF, and SmG in decreasing order of size. SmB has an alternatively spliced variant, SmB', and a very similar protein, SmN, replaces SmB'/B in certain (mostly neural) tissues. SmD was later discovered to be a mixture of three proteins, which were named SmD1, SmD2 and SmD3. These nine proteins (SmB, SmB', SmN, SmD1, SmD2, SmD3, SmE, SmF and SmG) became known as the Sm core proteins, or simply Sm proteins. The snRNAs are complexed with the Sm core proteins and with other proteins to form particles in the cell's nucleus called small nuclear ribonucleoproteins, or snRNPs. By the mid-1980s, it became clear that these snRNPs help form a large (4.8 MD molecular weight) complex, called the spliceosome, around pre-mRNA, excising portions of the pre-mRNA called introns and splicing the coding portions (exons) together. After a few more modifications, the spliced pre-mRNA becomes messenger RNA (mRNA) which is then exported from the nucleus and translated into a protein by ribosomes.
The snRNA U6 (unlike U1, U2, U4 and U5) does not associate with the Sm proteins, even though the U6 snRNP is a central component in the spliceosome. In 1999 a protein heteromer was found that binds specifically to U6, and consisted of seven proteins clearly homologous to the Sm proteins. These proteins were denoted LSm (like Sm) proteins (LSm1, LSm2, LSm3, LSm4, LSm5, LSm6 and LSm7), with the similar LSm8 protein identified later. In the bacterium Escherichia coli, the Sm-like protein HF-I encoded by the gene hfq was described in 1968 as an essential host factor for RNA bacteriophage Qβ replication. The genome of Saccharomyces cerevisiae (Baker's Yeast) was sequenced in the mid-1990s, providing a rich resource for identifying homologs of these human proteins. Subsequently, as more eukaryotes genomes were sequenced, it became clear that eukaryotes, in general, share homologs to the same set of seven Sm and eight LSm proteins. Soon after, proteins homologous to these eukaryote LSm proteins were found in Archaea (Sm1 and Sm2) and Bacteria (Hfq and YlxS homologs). The archaeal LSm proteins are more similar to the eukaryote LSm proteins than either are to bacterial LSm proteins. The LSm proteins described thus far were rather small proteins, varying from 76 amino acids (8.7 kD molecular weight) for human SmG to 231 amino acids (29 kD molecular weight) for human SmB. But recently, larger proteins have been discovered that include a LSm structural domain in addition to other protein structural domains (such as LSm10, LSm11, LSm12, LSm13, LSm14, LSm15, LSm16, ataxin-2, as well as archaeal Sm3).
Around 1995, comparisons between the various LSm homologs identified two sequence motifs, 32 nucleic acids long (14 amino acids), that were very similar in each LSm homolog, and were separated by a non-conserved region of variable length. This indicated the importance of these two sequence motifs (named Sm1 and Sm2), and suggested that all LSm protein genes evolved from a single ancestral gene. In 1999, crystals of recombinant Sm proteins were prepared, allowing X-ray crystallography and determination of their atomic structure in three dimensions. This demonstrated that the LSm proteins share a similar three-dimensional fold of a short alpha helix and a five-stranded folded beta sheet, subsequently named the LSm fold. Other investigations found that LSm proteins assemble into a torus (doughnut-shaped ring) of six or seven LSm proteins, and that RNA binds to the inside of the torus, with one nucleotide bound to each LSm protein.
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LSm
In molecular biology, LSm proteins are a family of RNA-binding proteins found in virtually every cellular organism. LSm is a contraction of 'like Sm', because the first identified members of the LSm protein family were the Sm proteins. LSm proteins are defined by a characteristic three-dimensional structure and their assembly into rings of six or seven individual LSm protein molecules, and play a large number of various roles in mRNA processing and regulation.
The Sm proteins were first discovered as antigens targeted by so-called anti-Sm antibodies in a patient with a form of systemic lupus erythematosus (SLE), a debilitating autoimmune disease. They were named Sm proteins in honor of Stephanie Smith, a patient who suffered from SLE. Other proteins with very similar structures were subsequently discovered and named LSm proteins. New members of the LSm protein family continue to be identified and reported.
Proteins with similar structures are grouped into a hierarchy of protein families, superfamilies, and folds. The LSm protein structure is an example of a small beta sheet folded into a short barrel. Individual LSm proteins assemble into a six or seven member doughnut ring (more properly termed a torus), which usually binds to a small RNA molecule to form a ribonucleoprotein complex. The LSm torus assists the RNA molecule to assume and maintain its proper three-dimensional structure. Depending on which LSm proteins and RNA molecule are involved, this ribonucleoprotein complex facilitates a wide variety of RNA processing including degradation, editing, splicing, and regulation.
Alternate terms for LSm family are LSm fold and Sm-like fold, and alternate capitalization styles such as lsm, LSM, and Lsm are common and equally acceptable.
The story of the discovery of the first LSm proteins begins with a young woman, Stephanie Smith, who was diagnosed in 1959 with systemic lupus erythematosus (SLE), eventually succumbing to complications of the disease in 1969 at the age of 22. During this period, she was treated at New York's Rockefeller University Hospital, under the care of Dr. Henry Kunkel and Dr. Eng Tan. As those with an autoimmune disease, SLE patients produce antibodies to antigens in their cells' nuclei, most frequently to their own DNA. However, Kunkel and Tan found in 1966 that Smith produced antibodies to a set of nuclear proteins, which they named the 'smith antigen' (Sm Ag). About 30% of SLE patients produce antibodies to these proteins, as opposed to double stranded DNA. This discovery improved diagnostic testing for SLE, but the nature and function of this antigen was unknown.
Research continued during the 1970s and early 1980s. The smith antigen was found to be a complex of ribonucleic acid (RNA) molecules and multiple proteins. A set of uridine-rich small nuclear RNA (snRNA) molecules was part of this complex, and given the names U1, U2, U4, U5 and U6. Four of these snRNAs (U1, U2, U4 and U5) were found to be tightly bound to several small proteins, which were named SmB, SmD, SmE, SmF, and SmG in decreasing order of size. SmB has an alternatively spliced variant, SmB', and a very similar protein, SmN, replaces SmB'/B in certain (mostly neural) tissues. SmD was later discovered to be a mixture of three proteins, which were named SmD1, SmD2 and SmD3. These nine proteins (SmB, SmB', SmN, SmD1, SmD2, SmD3, SmE, SmF and SmG) became known as the Sm core proteins, or simply Sm proteins. The snRNAs are complexed with the Sm core proteins and with other proteins to form particles in the cell's nucleus called small nuclear ribonucleoproteins, or snRNPs. By the mid-1980s, it became clear that these snRNPs help form a large (4.8 MD molecular weight) complex, called the spliceosome, around pre-mRNA, excising portions of the pre-mRNA called introns and splicing the coding portions (exons) together. After a few more modifications, the spliced pre-mRNA becomes messenger RNA (mRNA) which is then exported from the nucleus and translated into a protein by ribosomes.
The snRNA U6 (unlike U1, U2, U4 and U5) does not associate with the Sm proteins, even though the U6 snRNP is a central component in the spliceosome. In 1999 a protein heteromer was found that binds specifically to U6, and consisted of seven proteins clearly homologous to the Sm proteins. These proteins were denoted LSm (like Sm) proteins (LSm1, LSm2, LSm3, LSm4, LSm5, LSm6 and LSm7), with the similar LSm8 protein identified later. In the bacterium Escherichia coli, the Sm-like protein HF-I encoded by the gene hfq was described in 1968 as an essential host factor for RNA bacteriophage Qβ replication. The genome of Saccharomyces cerevisiae (Baker's Yeast) was sequenced in the mid-1990s, providing a rich resource for identifying homologs of these human proteins. Subsequently, as more eukaryotes genomes were sequenced, it became clear that eukaryotes, in general, share homologs to the same set of seven Sm and eight LSm proteins. Soon after, proteins homologous to these eukaryote LSm proteins were found in Archaea (Sm1 and Sm2) and Bacteria (Hfq and YlxS homologs). The archaeal LSm proteins are more similar to the eukaryote LSm proteins than either are to bacterial LSm proteins. The LSm proteins described thus far were rather small proteins, varying from 76 amino acids (8.7 kD molecular weight) for human SmG to 231 amino acids (29 kD molecular weight) for human SmB. But recently, larger proteins have been discovered that include a LSm structural domain in addition to other protein structural domains (such as LSm10, LSm11, LSm12, LSm13, LSm14, LSm15, LSm16, ataxin-2, as well as archaeal Sm3).
Around 1995, comparisons between the various LSm homologs identified two sequence motifs, 32 nucleic acids long (14 amino acids), that were very similar in each LSm homolog, and were separated by a non-conserved region of variable length. This indicated the importance of these two sequence motifs (named Sm1 and Sm2), and suggested that all LSm protein genes evolved from a single ancestral gene. In 1999, crystals of recombinant Sm proteins were prepared, allowing X-ray crystallography and determination of their atomic structure in three dimensions. This demonstrated that the LSm proteins share a similar three-dimensional fold of a short alpha helix and a five-stranded folded beta sheet, subsequently named the LSm fold. Other investigations found that LSm proteins assemble into a torus (doughnut-shaped ring) of six or seven LSm proteins, and that RNA binds to the inside of the torus, with one nucleotide bound to each LSm protein.