Function and synthesis of small nucleolar RNAs, …
Function and synthesis of small nucleolar ..
The phylogenetically conserved U14 small nucleolar RNA is required for processing of rRNA, and this function involves base pairing with conserved complementary sequences in 18S RNA. With a view to identifying other important U14 interactions, a stem-loop domain required for activity of Saccharomyces cerevisiae U14 RNAs (the Y domain) was first subjected to detailed mutational analysis. The mapping results showed that most nucleotides of the Y domain can be replaced without affecting function, except for loop nucleotides conserved among five different yeast species. Defective variants were then used to identify both intragenic and extragenic suppressor mutations. All of the intragenic mutations mapped within six nucleotides of the primary mutation, suggesting that suppression involves a change in conformation and that the loop element is involved in an essential intermolecular interaction rather than intramolecular base pairing. A high-copy extragenic suppressor gene, designated DBP4 (DEAD box protein 4), encodes an essential, putative RNA helicase of the DEAD-DEXH box family. Suppression by DBP4 (initially CA4 [T.-H. Chang, J. Arenas, and J. Abelson, Proc. Natl. Acad. Sci. USA 87:1571-1575, 1990]) restores the level of 18S rRNA and is specific for the Y domain but is not allele specific. DBP4 is predicted to function either in assembly of the U14 small nucleolar RNP or, more likely, in its interaction with other components of the rRNA processing apparatus. Mediating the interaction of U14 with precursor 18S RNA is an especially attractive possibility.
and localization of small nucleolar RNAs in ..
Lin T, Meng L, Lin T‐C, et al. (2014) Nucleostemin and GNL3L exercise distinct functions in genome protection and ribosome synthesis. Journal of Cell Science 127: 2302–2312.
our understanding of pre-rRNA processing in plants lags ..
From a panel ofsix miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) andtwo small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 wereidentified as the most stably expressed reference genes.
A novel function for small nucleolar RNAs.
For several decades the most extensively studied human DNA sequences were those generating messenger RNAs (mRNAs) which are used as templates for protein synthesis. The process decoding the genetic information from mRNAs to proteins is carried out by molecular machines named ribosomes and proteins are commonly perceived as essential molecules ensuring virtually all functions of cellular life. It has however become increasingly evident that a large fraction of the human DNA sequences produces a myriad of RNA molecules that are not translated into proteins. These so-called noncoding RNAs, whose existence was barely recognized a few years ago, are now considered as key players in a plethora of normal and pathological contexts. As a case in point, recent studies have identified a few Prader-Willi patients lacking a piece of noncoding DNA at a chromosomal location causally linked to the disease. Genetically speaking, it strongly suggests that the removal of this DNA segment plays an important and possibly direct role in the disease. Interestingly, this missing DNA portion produces many noncoding RNAs belonging to the family of C/D snoRNAs (SNORD116). Most of the C/D snoRNA members introduce chemical tags (methylations) onto ribosomes and thereby play pivotal role in ribosome synthesis and functions. Although identified 15 years ago, the exact molecular function of SNORD116 still remains a matter of active and lively debate. Today, we still do not know whether SNORD116 plays some roles in the production of ribosomes or whether it exerts other unsuspected roles. Thanks to the use of cells derived from Prader-Willi patients, the main goal of our project is to decipher the mode of action of this peculiar C/D snoRNA. Of particular interest, we propose to test the appealing notion that PWS may represent a novel example of the growing list of ribosomal diseases, i.e. diseases caused by abnormalities in ribosome synthesis and/or function. This type of basic research is essential to provide novel insights into the significance of SNORD116-mediated gene regulation, with important medical repercussions for our understanding of the etiology of the Prader-Willi Syndrome