Regulatory RNA

This book provides an introduction to and an overview of the field of regulatory RNA, focusing on the identification of regulatory elements and motifs in such RNA molecules. Central to the book is the use of appropriate techniques to identify regulatory RNA and regulatory motifs. The prospects for this new and expanding research field - understanding regulatory RNA elements and motifs - are also explored, including new developments, medical applications, and applications in other fields.

Contenu

1. An Introduction to Regulatory RNA Motifs.- A Short Guide to the Book.- A Look Back: RNA, the Magic Molecule.- RNA Motifs in RNA Information Flow and RNA Catalysis.- Fig. l.1. Regulatory motifs in mRNA metabolism.- Fig.1.2. Two examples for RNA motifs (RRE, TAR).- Regulation of Gene Expression at the Level of the RNA.- Time or space dependent information release by RNA.- Catalysis and processing involving RNA.- Ribonucleoproteins: Combination of RNA and proteins.- RNA Motifs as a Tool to Look for Conserved Function.- Perspective: Context Specificity of RNA Within the Cell.- 2. Instances of Functional RNA (An Overview).- The Different Types of RNA.- Table 2.1. The different types of RNA (overview).- General Nuclear RNA Binding Motifs and Nucleoproteins.- RNA and RNA Motifs Involved in Splicing.- RNA-protein interactions; Fig. 2.1, rRNA.- Fig. 2.2, snRNAs.- Further variants: Selfsplicing introns.- Trans-splicing.- Editing.- Motifs and RNAs Involved in Ribosomal RNA Processing.- Post-Transcriptional Regulatory Signals in m-RNA.- 5? UTR.- Regulatory signals in the open reading frame.- Translation regulated by non-mRNA.- Modified residues in eukaryotic messenger mRNA.- Correction of missing stop codons by ioSa-RNA or tm-RNA.- The 3? UTR of Messenger RNA.- 3? UTR of mRNA (Fig. 2.3, LOX mRNA).- Fig. 2.4,3? processing motifs.- Direct Regulation of Gene Expression.- Autoregulatory RNA.- Antisense RNA.- Regulation of prokaryotic operons.- Cytoplasmic RNA and Motifs.- Ribozymes and Their Motifs.- Viral RNA.- Other RNA Species.- A Catalogue of Regulatory RNA.- Table 2.2 a) Well-characterized motifs.- Table 2.2 b) Complex motifs.- Figures of Specific Motifs.- Se-Cys-mRNA; Fig. 2.5 transferrin receptor mRNA.- Fig. 2.6, developmental RNA motifs.- 5? UTR of mRNA, Fig. 2.7, eukaryotic iron-responsive-elements.- Fig. 2.8, prokaryotic translational repression, ?-mRNA.- Correcting Mrna translation (Fig.2.9, 10Sa RNA/tmRNA).- Splicing Fig. 2.10, simple and.- Fig. 2.10b, detailed pathway.- Fig. 2.11, U6/U4 and U6/U2.- Fig. 2.11b, U5 loop.- Fig. 2.12, Ui/U6/U2/pre-mRNA.- Fig. 2.13, alternative splice site selection.- trans-splicing Fig. 2.14, leader-mRNAs and reaction.- Small nucleolar RNAs; Fig. 2.15.- Fig. 2.16, guide snoRNAs.- Viral RNAs (Fig. 2.17).- Antisense RNAs (Fig. 2.18, motifs;).- Fig. 2.19, RNA III.- Catalytic RNAs (Fig. 2.20, hammerhead; Fig. 2.21, hairpin).- RNAse P (Fig. 2.22, RNA cage).- Substrates in Fig. 2.23.- Selfsplicing introns (group I Fig. 2.24, group II Fig. 2.25) 66,.- Selfsplicing intron reactions (Fig. 2.26) 68,.- Cytoplasmic RNAs (Fig. 2.27, 7S RNA from SRP).- Many RNA Motifs Together: RNA Viridae.- Table 2.3 Classification of different RNA viridae.- Table 2.4 Important protein motifs recognizing RNA.- Protein Motifs Pointing to Interacting RNA Structures.- Modified Nucleotides.- Table 2.5 RNA modifications.- Perspective: From Known Instances to New Ones.- 3. Experimental Identification of New Functional RNA.- Typical Settings.- Revealing RNAs as Key Players in Cellular Regulation.- Double-stranded RNA in growth arrest.- Revealing regulatory structures in developmental RNAs.- Identification of further translational regulatory mRNA motifs.- Affinity screens to reveal RNA interaction with proteins.- Crosslinking to reveal RNA interaction with proteins.- Direct Confirmation of RNA Functionality.- Detailed probing of an RNA motif.- Revealing the exact RNA structure.- Finding RNA Motifs for a Desired Task.- RNA SELEX experiments.- Further approaches to design and engineer RNA.- Perspective: Future Directions.- Fig. 3.1 SELEX method and subsequent genomic search.- 4. Computer Based and Theoretical Identification of Regulatory RNA.- Steps Involved in an RNA Motif Search.- Describe the motif.- Identify common features.- Derive a consensus pattern.- From the analytical description to the search program.- Fig. 4.1 Consensus patterns.- Program tests.- Analyzing program output.- Comparing promising candidate structures and known examples.- Experimental and further tests for remaining best candidate.- A Typical Example.- Specific Motif Search Programs.- General Purpose Search Programs.- Evaluation of the Search Result.- The best candidate RNA structures.- Table 4.1. Reducing the number of RNA candidate structures.- Generalized Searches for RNA Motifs.- Table 4.2. Some points to check during an RNA motif search.- Perspective: An Incentive.- 5. Functional RNA Interactions.- Control of Information Release.- Catalysis.- Metabolism.- Evolution.- Protein-RNA Interactions.- Table 5.1. Examples of RNA specific protein interactions.- Modified Nucleotides in RNA.- Identification of modified nucleotides.- Modified nucleotides as tools to modulate RNA metabolism.- (Table 5.2. Some examples).- Dynamics.- Further Development.- Nanopatterns using oligonucleotides.- Artificial evolution of peptides coupled to UNA SELEX.- Medical Implications: Curing RNA by Trans-Splicing.- Medical Implications: Antisense Approaches.- Ribozyme mediated RNA repair (Fig.5.1).- Medical Implications: Ribozymes.- Hammerheads.- Medical Manipulation of Ribonucleoprotein Particles.- Targeting of RNA, Fig. 5.2.- Suggestions for Further Therapies.- Perspectives.- New targets.- Translational inhibition.- Understanding RNA tools.- 6. Areas of Research on Regulatory RNA and Functional RNA Motifs.- The Splicing of Messenger RNA.- Process and RNA recognition.- ATAC introns (Fig. 6.1).- Trans-Splicing.- RNA Editing.- Mammalian RNA editing.- Fig. 6.2 RNA editing examples.- Editing in trypanosomes.- in slime-mold physarum.- in plant mitochondria and chloroplasts.- in hepatitis delta virus.- Ribosomal RNA Processing and Ribosome Biogenesis.- A focus of interest.- Ribosomal RNA processing steps.- Pathway (Fig. 6.3).- snoRNAs.- Nuclear RNA Transport.- Messenger RNA and Regulatory Motifs: The 5? Untranslated Region in mRNA.- Open Reading Frames in mRNA.- Is a cDNA sequence complete?.- Regulation of ORF translation by transfer-RNA redundancy.- The 3? Untranslated Region in mRNA.- 3? UTR in parasites.- Se-Cys mRNAs.- Motif searches and a SELEX approach.- Detailed analysis of a complex RNA stability motif in the 3? UTR.- Polyadenylation signals.- Developmental differentiation signals in the 3? UTR.- Three hybrid screening system (Fig. 6.4).- Developmental localization signals in the 3? UTR.- Catalytic RNAs.- Selfsplicing introns.- Viral RNAs.- Perspective: New Interesting RNA Structures.- Cytoplasmic RNAs.- XIST, (X chromosome inactivation) RNA.- H19 RNA and imprinting.- C. elegans lin-4 RNA.- Telomerases: maintaining the ends of the chromosomes.- Fig. 6.5. Telomerase RNA and telomers.- Small RNAs in E. coli.- OxyS (Fig. 6.6).- 7. Future Research.- Splicing.- Editing, Trans-Splicing and Beyond.- Ribosomal RNA and Cofactors.- Signals in the mRNA.- Antisense RNA.- Biotechnological Applications.- Conclusion.- Alphabetical References.