Y- RNA

Y-RNA

Y RNAs have been found in all vertebrates in which they have been studied, as well as in C. elegans and the bacterium D. radiodurans. There are usually 1-4 Y RNAs present in a given species, and these Y RNA genes are usually found within a cluster on the same chromosome. They contain their own promoters and the distance between the genes as well as their order is well-conserved .

Studies surrounding the evolution of Y RNA genes indicate that a single ancestral Y RNA duplicated to give rise to two distinct Y RNA genes, which further gave rise to four Y RNA genes in the order Y5-Y4-Y3-Y1. The presence of less than 4 Y RNAs in some species suggests that some of these genes were lost through evolution .

Northern blot analysis of various vertebrate Y RNA samples probed with human Y cDNA showed the Y3 is the most conserved, Y1 is less conserved than Y3, and Y4 and Y5 are the least conserved.

significant partner RNAs or proteins: 

The RoRNP consists of two proteins that interact directly with Y RNA, Ro60 and La.  La contains an amino terminal RNA binding region (RNP-80) and carboxy terminus phosphorylation sites that modulate RNA binding ability. La binds to an oligouridine stretch found at the 3' end of Y RNA. Ro60 also contains an amino terminal RNA binding domain (RNP-80), and its overall conformation is also important for proper binding to Y RNA. Ro60 binds to the distal stem region of Y RNA at conserved nucleotides found within a bulged structure. Interaction of La and Ro60 with Y RNA have been proposed to protect and stabilize Y RNA, as well as aid in its translocation from the nucleus to the cytoplasm .  As a general mechanism, Y RNA binding to La and Ro may inhibit the chaperone activity of these proteins.

hY1 and hY3 have also been shown to interact more transiently with hnRNP K and I and nucleolin in the loop region. The significance of this is not as well studied, but may involve regulation of the chaperone activities of these RNPs and proteins .

Y RNA functionally interacts with components of the DNA replication machinery, such as RPA and PCNA.

mechanism of action: 

Studies revealing the structure of Ro60 suggest that Y RNA has the ability to inhibit Ro60's chaperone activity by binding to it . Ro60 binds misfolded RNAs via the external region of its N-terminal circular domain. 3' single stranded regions of bound RNA are threaded through the central cavity of this circle, and this is thought to be crucial for targeting misfolded RNAs for degradation or possibly for facilitating refolding. Y RNAs bind Ro60 at this same external region of the circular domain via their stem region. This sterically hinders the ability of misfolded RNAs to bind Ro60, implicating Y RNAs as a repressor of Ro60 activity. Similarly, regions in Ro60 required for its translocation to the nucleus seem to be masked by binding of Y RNA, and binding of Y RNA to hnRNP K and I has been shown to inhibit their splicing related chaperone activities , 

The mechanism for RoRNP mediated resistance to UV irradition in D. radiodurans and mouse ES cells is unknown.

The mechanism for Y RNA's role in DNA replication is unknown. It does not appear that Y RNA functions as a primer, and it does not involve interaction of Y RNA with Ro60.

cellular functions: 

Y RNAs are part of the RoRNP, which also contains the proteins Ro60 and La. Ro60 acts as a molecular chaperone that regulates proper folding and assembly of small, non-coding RNAs by binding them. For example, roles for Ro60 in regulating the maturation of U2 snRNAs, 23S rRNAs, and 5s rRNAs has been observed in mouse ES cells, D. radiodurans, and X. laevis, respectively . La also appears to have chaperone activities involved in regulating processing of RNAs and assembly of RNPs . Binding of Y RNA to Ro60 and La is thought to repress these chaperone activities . Similarly, hY1 and hY3 may inhibit chaperone activities of the more transient interacting partners, heterogeneous nuclear RNP (hnRNP) K and I . The most recent reports also suggest Y RNA regulates the localization of Ro60. While the functional roles of the different Y RNAs have not been elucidated, it has been proposed that their structural differences may confer the ability of the RoRNP to recognize different types of misfolded RNAs.

Studies in mammalian cells and D. radiodurans suggest that the Ro60 and Y RNA may also be important in resistance to UV irradiation. Increases in RoRNP particles (i.e. increases in levels of Ro and binding of Y RNA to Ro) in D. radiodurans and increases in the nuclear localization of RoRNPs in mouse embryonic stem cells occurs in response to UV irradiation, and inhibition either of these processes decreased survival, implicating a role for RoRNPs and Y RNAs in UV resistance, however the mechanism behind this is not known.

Y RNA has also been shown to have an essential role in DNA replication. Studies using isolated human nuclei in cell free DNA replication systems were used to show that hY1, hY3, hY4, or hY5 is required but not sufficient for replication in this system. This data also showed that there is redundancy among the hY RNAs in regulating DNA replication. These results were supported by in vitro data showing that siRNA knockdown of hY1 in HeLa cells decreased proliferation.