RNA Motif
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An RNA motif is a description of a group of
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
s that have a related structure. RNA motifs consist of a pattern of features within the primary sequence and
secondary structure Protein secondary structure is the local spatial conformation of the polypeptide backbone excluding the side chains. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...
of related RNAs. Thus, it extends the concept of a
sequence motif In biology, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and usually assumed to be related to biological function of the macromolecule. For example, an ''N''-glycosylation site motif can be defined as ''A ...
to include RNA secondary structure. The term "RNA motif" can refer both to the pattern and to the RNA sequences that match it.


Descriptions of RNAs motifs

RNA motifs can be described in two main forms: a
multiple sequence alignment Multiple sequence alignment (MSA) is the process or the result of sequence alignment of three or more biological sequences, generally protein, DNA, or RNA. These alignments are used to infer evolutionary relationships via phylogenetic analysis an ...
or an explicit search pattern. An alignment is usually augmented with a consensus secondary structure, i.e. the structure that is common to all or most RNAs. The sequences in the alignment then implicitly define a pattern of conservation that can, for example, be used to find additional examples of the RNA. This search strategy is implemented by, among others, the Infernal software package. The
Rfam Rfam is a database containing information about non-coding RNA (ncRNA) families and other structured RNA elements. It is an annotated, open access database originally developed at the Wellcome Trust Sanger Institute in collaboration with Janel ...
database is a collection of multiple sequence alignments that define a large subset of reliably known RNA motifs and associated information. Its data can be used with the Infernal software to find examples of such RNAs in sequence databases, e.g.
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
sequences. Alternatively, RNA motifs can also be described using explicit search patterns, which define specific primary sequence patterns combined with constraints of where helices should form. Such patterns can be used to find matching subsequences in a large sequence database. Several software packages implement such a search, e.g. RNArobo and RNAmotif.


Discovery of novel RNA motifs

Many methods to discover novel RNAs use a comparative approach, in which different sequences are analyzed together in order to detect characteristic signals of a conserved RNA. When such methods are successful, the resulting novel conserved RNA can be viewed as an RNA motif, expressed using an alignment or a pattern. An early example is the RNA motif based around the
T-box T-box refers to a group of transcription factors involved in embryo, embryonic limb development, limb and heart development. Every T-box protein has a relatively large DNA-binding domain, generally comprising about a third of the entire protein ...
, which in 1993 was determined to be associated with aminoacyl-tRNA synthetase genes. The mechanism by which this RNA motif regulates genes was later demonstrated, thus establishing the functional importance of the RNA motif. Later, in 1997, a conserved RNA motif called the B12-box was detected upstream of genes related to B12 metabolism. This RNA motif was later found to correspond to a part of a
riboswitch In molecular biology, a riboswitch is a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in Translation (biology), production of the proteins encoded by the mRNA. Thus, an mRNA that contains a ribo ...
that binds the co-factor
adenosylcobalamin Adenosylcobalamin (AdoCbl), also known as coenzyme B12, cobamamide, and dibencozide, is one of the biologically active forms of vitamin B12. Adenosylcobalamin participates as a cofactor in radical-mediated 1,2-carbon skeleton rearrangements. T ...
, which is often called the cobalamin riboswitch. (Later variants were shown to bind other cobalamin derivatives.) Many other examples of RNA motifs whose functions were later determined are known, especially in the context of riboswitches. However, other types of RNA motifs have been functionally characterized, such as bacterial sRNAs like the 6C RNA, which was discovered as a motif in 2007 and functionally characterized in 2016, or
ribozyme Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to Catalysis, catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozy ...
s like the twister ribozyme, which was detected as an RNA motif and functionally characterized in the same publication.


References

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