Conserved Nucleotide Elements In Ribosomal RNA
AssigneeBrown University
InventorsSusan A. Gerbi, Stephen M. Doris, Deborah R. Smith, Julia Beamesderfer, Benjamin J. Raphael
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Abstract
The present invention relates to a method of determining conserved ribosomal RNA (rRNA) nucleotide motifs that are specific to one domain of life, Eukarya, Bacteria, or Archaea, and degenerate in at least one other domain of life. The invention also relates to a method of determining conserved ribosomal RNA (rRNA) nucleotide motifs that are specific to one subgroup and degenerate in another subgroup within a domain of life or for a subset group within a domain of life. The invention relates to a method of identifying a compound that is a domain-specific or subgroup-specific ribosomal RNA inhibitor.
Claims42
A method of determining conserved ribosomal RNA (rRNA) nucleotide motifs that are specific to one domain of life and degenerate in at least one other domain of life, comprising the steps of:
- a) generating a data set of a single copy of full length rRNA sequences, including a greater than or equal to about 70% identity to a sequence of about 15 nucleotides proximate to the 3′ end of the small subunit ribosomal RNA or the large ribosomal subunit RNA, for each of the Eukarya, Bacteria or Archaea domains of life or a merger of the domains of life or for a subgroup within a domain of life;
- b) filtering the data set against at least one representative structural sequence from each of the Eukarya, Bacteria or Archaea domains of life to align all sequences to the representative secondary structure;
- c) using overlapping windows of at least about 6 nucleotides for each of the Eukarya, Bacteria or Archaea domains of life to obtain rRNA nucleotide sequences that have an informational content score of greater than or equal to about 11 and a nucleotide sequence identity of greater than about 90%, with subsequent merger of the about 6 nucleotide stretches that overlap to generate a collection of rRNA nucleotide motifs in Eukarya (eCNE=conserved nucleotide elements in Eukarya), rRNA nucleotide motifs in Bacteria (bCNE=conserved nucleotide elements in Bacteria), rRNA nucleotide motifs in Archaea (aCNE=conserved nucleotide elements in Archaea), or in any subgroup within a domain of life;
- and
- d) determining conserved rRNA nucleotide motifs of at least about 6 nucleotides in length that are specific for one domain of life and degenerate in at least one other domain of life from the collection of rRNA nucleotide motifs in Eukarya (domain-specific d-s eCNE), rRNA nucleotide motifs in Bacteria (domain-specific d-s bCNE), and rRNA nucleotide motifs in Archaea (domain-specific d-s aCNE).
A method of determining conserved ribosomal RNA (rRNA) nucleotide motifs that are specific to one subgroup and degenerate in at least one other subgroup within Eukarya, comprising the steps of:
- a) generating a data set of a single copy of full length rRNA sequences, including a greater than or equal to about 70% identity to a sequence of about 15 nucleotides near the 3′ end of the small subunit ribosomal RNA or the large ribosomal subunit RNA, for the Eukarya domain of life or for a subset group with a domain of life;
- b) filtering the data set against at least one representative structural sequence from the subgroup within Eukarya to align all sequences to the representative secondary structure;
- c) using overlapping windows of at least about 6 nucleotides for each of the subgroups within Eukarya to obtain rRNA nucleotide sequences that have an informational content score of greater than or equal to about 11 and a nucleotide sequence identity of greater than about 90%, with subsequent merger of the about 6 nucleotide stretches that overlap to generate a collection of rRNA nucleotide motifs in the subgroup within Eukarya;
- and
- d) determining conserved rRNA nucleotide motifs of at least about 6 nucleotides in length that are specific for one subgroup within Eukarya and degenerate in at least one other subgroup within Eukarya from the collection of rRNA nucleotide motifs in the subgroup within Eukarya.
A method of determining conserved ribosomal RNA (rRNA) nucleotide motifs that are specific to one subgroup and degenerate in at least one other subgroup within Bacteria, comprising the steps of:
- a) generating a data set of a single copy of full length rRNA sequences, including a greater than or equal to about 70% identity to a sequence of about 15 nucleotides near the 3′ end of the small subunit ribosomal RNA or the large ribosomal subunit RNA, for the Bacteria domain of life or for a subset group within a domain of life;
- b) filtering the data set against at least one representative structural sequence from the subgroup within Bacteria to align all sequences to the representative secondary structure;
- c) using overlapping windows of at least about 6 nucleotides for each of the subgroups within Bacteria to obtain rRNA nucleotide sequences that have an informational content score of greater than or equal to about 11 and a nucleotide sequence identity of greater than about 90%, with subsequent merger of the about 6 nucleotide stretches that overlap to generate a collection of rRNA nucleotide motifs in the subgroup within Bacteria;
- and
- d) determining conserved rRNA nucleotide motifs of at least about 6 nucleotides in length that are specific for one subgroup within Bacteria and degenerate in at least one other subgroup within Bacteria from the collection of rRNA nucleotide motifs in the subgroup within Bacteria.
A method of determining conserved ribosomal RNA (rRNA) nucleotide motifs that are specific to one subgroup and degenerate in at least one other subgroup within Archaea, comprising the steps of:
- a) generating a data set of a single copy of full length rRNA sequences, including a greater than or equal to about 70% identity to a sequence of about 15 nucleotides near the 3′ end of the small subunit ribosomal RNA or the large ribosomal subunit RNA, for the Archaea domain of life or for a subset group within a domain of life;
- b) filtering the data set against at least one representative structural sequence from the subgroup within Archaea to align all sequences to the representative secondary structure;
- c) using overlapping windows of at least about 6 nucleotides for each of the subgroups within Archaea to obtain rRNA nucleotide sequences that have an informational content score of greater than or equal to about 11 and a nucleotide sequence identity of greater than about 90%, with subsequent merger of the about 6 nucleotide stretches that overlap to generate a collection of rRNA nucleotide motifs in the subgroup within Archaea;
- and
- d) determining conserved rRNA nucleotide motifs of at least about 6 nucleotides in length that are specific for one subgroup within Archaea and degenerate in at least one other subgroup within Archaea from the collection of rRNA nucleotide motifs in the subgroup within Archaea.
Dependencies are inferred from the claim text.