Y RNAs are small

non-coding RNA A non-coding RNA (ncRNA) is a functional RNA molecule that is not Translation (genetics), translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally imp ...

s. They are components of the Ro60 ribonucleoprotein particle which is a target of autoimmune antibodies in patients with

systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...

. They are also reported to be necessary for

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...

through interactions with

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

and initiation proteins. However, mouse embryonic stem cells lacking Y RNAs are viable and have normal cell cycles.

Structure

These small RNAs are predicted to fold into a conserved stem formed by the RNA's 3′ and 5′ ends and characterized by a single bulged

cytosine Cytosine () (symbol C or Cyt) is one of the four nucleotide bases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attac ...

, which are the known requirements for Ro binding.

Function

Two functions have been described for Y RNAs in the literature: As a repressor of Ro60, and as an initiation factor for

. Mutant human Y RNAs lacking the conserved binding site for Ro60 protein still support DNA replication, indicating that binding to Ro protein and promoting DNA replication are two separable functions of Y RNAs. Although Y RNA-derived small RNAs are similar in size to microRNAs, it has been shown that these Y RNA fragments are not involved in the microRNA pathway. YRNA-Ro60

Ro60 Inhibition

In its free state, Ro binds to a variety of misfolded RNAs including misfolded 5S rRNAs, and is thought to act as some sort of quality control mechanism.

Crystal structure In crystallography, crystal structure is a description of ordered arrangement of atoms, ions, or molecules in a crystalline material. Ordered structures occur from intrinsic nature of constituent particles to form symmetric patterns that repeat ...

s of Ro complexed either with Y RNA or another RNA showed that Ro binds single-stranded 3′ ends of RNAs relatively nonspecifically, whereas Y RNA binds specifically at a second site that regulates access of other RNAs. In '' Deinococcus'', free Ro has also been shown to function in 23S

rRNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...

maturation. In ''Deinococcus'',

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It i ...

s lacking Y RNA are viable, and Y RNA appears to be unstable except when complexed with Ro.

DNA replication initiation

Human Y RNAs are functionally required for

. Biochemical

fractionation Fractionation is a separation process in which a certain quantity of a mixture (of gasses, solids, liquids, enzymes, or isotopes, or a suspension) is divided during a phase transition, into a number of smaller quantities (fractions) in which t ...

and reconstitution experiments have established a functional requirement of human Y RNAs for

chromosomal A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most importa ...

DNA replication in isolated

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

cell nuclei ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' and specific degradation of human Y RNAs inhibits DNA replication ''in vitro'', and in intact cells ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

''. Y RNA function is thought to be mediated via interactions with

and initiation proteins (including the

origin recognition complex In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes and archaea in an Adenosine triphosphate, ATP-dependent manner to origins of replication. The subunits of this ...

)

In human pathology

Y RNAs are overexpressed in some human

tumour A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...

s and are required for cell proliferation and small, microRNA-sized breakdown products may be involved in autoimmunity and other pathological conditions. Recent work has demonstrated that Y RNAs are modified at their 3′ end by the non-canonical poly(A) polymerase PAPD5, and the short oligo(A) tail added by PAPD5 is a marker for 3′ end processing by the ribonuclease PARN/EXOSC10 or for degradation by the exonuclease DIS3L. Since PARN deficiency causes a severe form of the bone marrow disease Dyskeratosis Congenita as well as pulmonary fibrosis, it is possible that defects in Y RNA processing contribute to the severe pathology observed in these patients.

Species distribution

Presumptive Y RNA and Ro protein homologs have been found in

eukaryotes The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...

and

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

Humans

Humans appear to have four Y RNAs, named hY1, hY3, hY4 and hY5 and also a large number of pseudogenes.

''C. elegans''

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...

'' has one, named CeY RNA and a large number of sbRNAs that are postulated to also be Y RNA homologues.

''D. radiodurans''

The radiation-resistant bacterium '' Deinococcus radiodurans'' encodes a homolog of Ro called rsr ("Ro sixty related"), and at least four small RNAs accumulate in ''Deinococcus'' under conditions where rsr expression is induced ( UV irradiation); one of these RNAs appears to be a Y RNA homolog. In ''Deinococcus radiodurans'' Rsr is tethered via Y RNA to the exoribonuclease PNPase and channels single-stranded RNA into the PNPase cavity. Rsr and Y RNA enhance degradation of structured RNAs by PNPase. This role could be conserved, as Rsr and ncRNAs called YrlA and YrlB (Y RNA like) also associate with PNPase in an evolutionary distant bacterium ''Salmonella Typhimurium''.

References

External links

* {{Nucleic acids Non-coding RNA