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1 | (48) |
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1.1 The Life Cycle of an Eukaryotic mRNA Molecule |
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1 | (4) |
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5 | (2) |
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1.3 RNA-Binding Proteins and Disease |
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7 | (3) |
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1.4 The RNA-Binding Protein LIN28 |
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10 | (5) |
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1.4.1 Lin28 Inhibits miRNA Let-7 Biogenesis |
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11 | (1) |
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1.4.2 Mechanism of Lin28-Let-7 Recognition |
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12 | (1) |
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1.4.3 The Functional Role of Lin28 in Stem Cell Biology, Cancer and Metabolism |
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12 | (2) |
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1.4.4 Lin28 Can Function Independent of Let-7 |
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14 | (1) |
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1.4.5 Lin28 as a Direct Regulator of Mrna Translation |
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14 | (1) |
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15 | (3) |
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1.6 Cis-regulatory Sequence Elements in Eukaryotes |
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18 | (9) |
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1.6.1 Upstream Open Reading Frames (uORFs) |
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18 | (1) |
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1.6.2 Internal Ribosome Entry Sites (IRESs) |
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19 | (1) |
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1.6.3 Ribosome Frameshift Signals (RFSs) |
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20 | (1) |
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1.6.4 Splicing Regulatory Elements (SREs) |
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21 | (1) |
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1.6.5 Iron Response Elements (IREs) |
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22 | (1) |
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1.6.6 RNA Methylation Sites |
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22 | (2) |
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1.6.7 AU-Rich Elements (AREs) |
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24 | (1) |
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25 | (1) |
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1.6.9 Polyadenylation Signals (PASs) |
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26 | (1) |
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1.7 Target Site Identification of Post-transcriptional Regulators |
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27 | (22) |
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1.7.1 From the Study of a Single RBP to the `Post-transcriptional Regulatome' |
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32 | (1) |
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33 | (16) |
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2 Mapping Regulatory Interactions of the RNA-Binding Protein LIN28B |
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49 | (12) |
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2.1 PAR-CLIP Reproducibly Identifies Thousands of Human RNAs Directly Bound by LIN28B |
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49 | (2) |
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2.2 LIN28B Binds to Let-7 Precursors and Protein Coding Transcripts |
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51 | (2) |
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2.3 Target Transcripts Are Enriched for a RGGSWG Consensus Motif |
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53 | (1) |
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2.4 Individual Domain PAR-CLIP Enables Characterization of Domain Specific Target Interactions |
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54 | (2) |
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2.5 LIN28B Enhances Protein Production of mRNA Target Transcripts |
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56 | (2) |
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2.6 LIN28B Controls Core Cell Cycle Regulators |
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58 | (3) |
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59 | (2) |
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3 Exploring the Sequence Space Contacted by the Ensemble of RNA-Binding Proteins |
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61 | (12) |
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3.1 Protein Occupancy Profiling Provides Catalog of Protein-mRNA Contact Sites |
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62 | (2) |
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3.2 Protein Occupancy Profiling Recapitulates AGO Binding Pattern at miRNA Target Sites |
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64 | (2) |
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3.3 Protein Occupancy Profiling Reveals Widespread and Conserved Protein-mRNA Contacts |
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66 | (2) |
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3.4 Putative RNA Cis-regulatory Elements Overlap with Trait/Disease-Associated Polymorphisms |
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68 | (1) |
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3.5 The Impact of Actively Translating Ribosomes on Protein Occupancy Profiles |
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68 | (5) |
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71 | (2) |
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4 Revealing Cell-Type Specific Differences in Protein Occupancy on RNA |
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73 | (16) |
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4.1 Protein Occupancy Profiling in MCF7 Cells |
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73 | (1) |
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4.2 Comparing Gene Expression and Protein Occupancy Profiles in MCF7 and HEK293 Cells |
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74 | (3) |
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4.3 Differential Protein Occupancy Profiling Based on T-C Transitions |
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77 | (1) |
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4.4 Identification of Differentially Occupied RNA Regions Between MCF7 and HEK293 Cells |
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78 | (3) |
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4.5 Differentially Occupied Positions Show Distinct Secondary-Structure Characteristics and Overlap with Binding Sites of Known RBPs |
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81 | (4) |
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4.6 Transcripts with Increased Protein Occupancy in MCF7 Cells Show Elevated mRNA Half-Lives |
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85 | (4) |
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86 | (3) |
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89 | (32) |
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5.1 PAR-CLIP and iDo-PAR-CLIP: Challenges and Considerations |
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90 | (3) |
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5.1.1 PAR-CLIP Depends on Effective Metabolic Labeling of RNA |
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90 | (1) |
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5.1.2 Potential Biases in CLIP and PAR-CLIP Experiments |
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91 | (1) |
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5.1.3 Individual Domain PAR-CLIP: Asymmetry Is Key |
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92 | (1) |
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5.2 Controlling Background in CLIP and PAR-CLIP Experiments |
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93 | (2) |
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5.2.1 The Advantage of Combining Old and New Ways to Capturing RNA Targets |
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93 | (1) |
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5.2.2 The Challenge of the Next Generation: Controlling Sequencing Depth |
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94 | (1) |
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5.3 Transcriptome-Wide Identification of LLN28B-Bound RNA Targets |
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95 | (6) |
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5.3.1 Multiple Studies Identify Lin28A and Lin28B-Bound RNA Targets in Different Systems |
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95 | (2) |
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5.3.2 From Transcriptome-Wide Lin28 Binding Sites to a Model of mRNA Recognition |
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97 | (2) |
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5.3.3 A Direct Role for LIN28B in Regulating Protein Synthesis |
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99 | (2) |
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5.4 The Emerging Picture: Protein Production Is Regulated by Lin28 Through Let-7-Dependent and Let-7-Independent Mechanisms |
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101 | (2) |
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5.4.1 Let-7-Dependent Effects of Lin28 |
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101 | (1) |
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5.4.2 Let-7-Independent Effects of Lin28 |
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102 | (1) |
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5.4.3 Merging Two Worlds: MRNA Translation Is Directly Regulated by Lin28 and Let-7 |
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102 | (1) |
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5.5 Transcriptome-Wide Protein Occupancy Profiling |
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103 | (18) |
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5.5.1 Protein Occupancy Profiling and the mRNA Bound Proteome |
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104 | (1) |
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5.5.2 Characteristics of Protein Occupancy Profiles |
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105 | (2) |
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5.5.3 Protein Occupancy and mRNA-Expression: A Distant Relationship? |
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107 | (1) |
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5.5.4 Protein Occupancy and Ribosomes: An Unexpected Crosslinking Bias |
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107 | (2) |
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5.5.5 Differential Protein Occupancy: From Crosslinks to Regulators |
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109 | (2) |
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5.5.6 Transcriptome-Wide and Unbiased Identification of Novel Cis-acting RNA Elements |
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111 | (1) |
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5.5.7 Lessons from the RBP-Bound mRNA Sequence Space |
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111 | (1) |
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5.5.8 Application of Protein Occupancy Profiling and Future Directions |
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112 | (2) |
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114 | (7) |
Supplementary Information |
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121 | |