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Transcript of Transcripción Alberts 2014.pdf
Molecular Biologyof the Cell
Sixth Edition
Chapter 6
How Cells Read the Genome:
From DNA to Protein
Copyright © Garland Science 2015
Alberts • Johnson • Lewis • Morgan • Raff • Roberts • Walter
CHAPTER CONTENTS
FROM DNA TO RNA
FROM RNA TO PROTEIN
THE RNA WORLD AND THE ORIGINS OF LIFE
Introduction
Introduction
FROM DNA TO RNA
• Introduction
Introduction
FROM DNA TO RNA
• RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
RNA Molecules Are Single-Stranded
FROM DNA TO RNA
• Transcription Produces RNA Complementary to One Strand of DNA
Transcription Produces RNA Complementary to One Strand of DNA
FROM DNA TO RNA
• RNA Polymerases Carry Out Transcription
RNA Polymerases Carry Out Transcription
RNA Polymerases Carry Out Transcription
FROM DNA TO RNA
• Cells Produce Different Categories of RNA Molecules
Cells Produce Different Categories of RNA Molecules
FROM DNA TO RNA
• Signals Encoded in DNA Tell RNA Polymerase Where to Start and Stop
Signals Encoded in DNA Tell RNA Polymerase Where to Start and Stop
Signals Encoded in DNA Tell RNA Polymerase Where to Start and Stop
Signals Encoded in DNA Tell RNA Polymerase Where to Start and Stop
Signals Encoded in DNA Tell RNA Polymerase Where to Start and Stop
FROM DNA TO RNA
• Transcription Start and Stop Signals Are Heterogeneous in Nucleotide Sequence
Transcription Start and Stop Signals Are Heterogeneous in Nucleotide Sequence
Transcription Start and Stop Signals Are Heterogeneous in Nucleotide Sequence
Transcription Start and Stop Signals Are Heterogeneous in Nucleotide Sequence
Transcription Start and Stop Signals Are Heterogeneous in Nucleotide Sequence
Transcription Start and Stop Signals Are Heterogeneous in Nucleotide Sequence
FROM DNA TO RNA
• Transcription Initiation in Eukaryotes Requires Many Proteins
Transcription Initiation in Eukaryotes Requires Many Proteins
Las 3 RNA polimerasas son estructuralemente similares entre ellas (y con la RNA polimerasa bacteriana)
comparten subunidades pero transcriben diferente tipo de genes.
La RNA polimerasa II tiene muchas similitudes estructurales con la RNA polimerasa bacteriana, pero también
existen diferencias importantes:1- La RNA polimerasa bacteriana requiere solo de una proteína adicional para la iniciación de la transcripción,la RNA polimerasa II requiere de muchas proteínas adicionales,llamadas factores de transcripción generales.2- La iniciación de la transcripción en eucariotes trata con el empacamiento de DNA en nucleosomas yen cromatina, una estructura altamente organizada, ausente en el cromosoma bacteriano.
Transcription Initiation in Eukaryotes Requires Many Proteins
FROM DNA TO RNA
• RNA Polymerase II Requires a Set of General Transcription Factors
RNA Polymerase II Requires a Set of General Transcription Factors
Los factores de transcripción generales
ayudan a posicionar a la RNA
polimerasa correctamente sobre el
promotor, ayudan a separar la doble
hélice para que comience la
transcripción y a liberar a la RNA
polimerasa del promotor al modo de
elongación, una vez que inició la
transcripción. Se dice que los factores
son generales porque se requieren en
casi todos los promotores de la RNApol
II.
RNA Polymerase II Requires a Set of General Transcription Factors
RNA Polymerase II Requires a Set of General Transcription Factors
Secuencias consenso que se han encontrado cerca del inicio de la transcripción
RNA Polymerase II Requires a Set of General Transcription Factors
FROM DNA TO RNA
• Polymerase II Also Requires Activator, Mediator, and Chromatin-Modifying Proteins
• La transcripción por la RNA pol II en una célula eucarionte es más compleja y requiere muchas más proteínas.
• 1- requiere de proteínas regulatorias - activadores transcripcionales, los cuales deben unirse a secuencias de DNA específicas y ayudan a atraer la RNA pol II al punto de inicio de la transcripción
• 2- la iniciación de la transcripción en eucariontes in vivo requiere de un complejo protéico - mediador, que permite que las proteínas activadoras se comuniquen con la RNA pol II y con los factores de transcripción generales.
• 3- la iniciación de la transcripción en eucariontes requiere el reclutamiento local de las enzimas modificadoras de la cromatina, incluyendo los complejos remodeladores de la cromatina y las enzimas modificadoras de las histonas.
Polymerase II Also Requires Activator, Mediator, and Chromatin-Modifying Proteins
FROM DNA TO RNA
• Transcription Elongation in Eukaryotes Requires Accessory Proteins
FROM DNA TO RNA
• Transcription Creates Superhelical Tension
Transcription Creates Superhelical Tension
Transcription Creates Superhelical Tension
Transcription Creates Superhelical Tension
Transcription Creates Superhelical Tension
FROM DNA TO RNA
• Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
El factor de transcripción TFIIH fosforila el
CTD de la RNA polimerasa II, indicando la
transición de la iniciación a la elongación. Las
proteínas necesarias para el capping, para el
procesamiento y para la poliadenilación del pre
RNAm reconocen las diferentes formas
fosforiladas del CTD de la RNA polimerasa II.
De lo que se trata es que las proteínas
encargadas del capping, de procesamiento del
pre RNAm y de la poliadenilación del RNAm
se acerquen a sus sitios de acción en el
RNAm precursor conforme se transcriben
durante la elongación.
la transcripción en eucariontes está acoplada al
procesamiento del RNA
Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
Transcription Elongation in Eukaryotes Is Tightly Coupled to RNA Processing
Conforme la polimerasa transcribe, va cargando proteínas de procesamiento del preRNAm en su cola (CTD)las cuales va a transferir al RNAm naciente. La proteína de capping se une primero al CTD de la RNA polimerasa
cuando está fosforilada en la ser5 del hepta-repetido, una vez que la iniciación de la transcripción está avanzada. Esto asegura que la molécula de RNA se modifique eficientemente en el 5’.Posteriormente, el CTD de la polimerasa se fosforila en la ser2 por una kinasa asociada con las proteínas de elongación,y eventualmente se desfosforila en la ser5. Estas modificaciones en el CTD de la polimerasa van a atraer otras proteínasde procesamiento para que actúen en el RNAm conforme va emergiendo de la RNA polimerasa.Sin embargo son muchas las enzimas que procesan el RNAm, y no todas viajan con la RNA polimerasa.Pero una vez que alguna proteína crítica del procesamiento se ha transferido a la molécula de RNAm,
va a atraer al resto del complejo proteíco para que procese la molécula de RNA.
FROM DNA TO RNA
• RNA Capping Is the First Modification of Eukaryotic Pre-mRNAs
RNA Capping Is the First Modification of Eukaryotic Pre-mRNAs
3 enzimas, que actúan sucesivamente, realizan la reacción de capping.
Una fosfatasa elimina un fosfato del extremo 5’ nasciente del RNA,
una guanidiltransferasa añade un GMP en 5’-5’,
y una metil transferasa metila la guanosina.
Las 3 se unen al CTD fosforilado en la ser5,
y por lo tanto están listas para modificar el extremo 5’ naciente
al momento que emerge de la polimerasa.
El cap 5’ metilado significa un extremo 5’ de un RNAm,
y esto le permite a la célula distinguir entre otros tipos de moléculas
de RNA presentes en la célula. La RNA polI y la RNA pol III no
producen transcritos con cap, en parte porque no tienen CTD.
Cual es la función del cap en el extremo 5’ del RNAm?
En el núcleo, el cap del 5’ del RNAm se une a un complejo protéico (CBC)
que le ayuda al mensajero a procesarse y exportarse adecuadamente.
También el cap tiene una función en la traducción.
FROM DNA TO RNA
• RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs
RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs
RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs
RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs
RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs
RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs
RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs
RNA Splicing Removes Intron Sequences from Newly Transcribed Pre-mRNAs
FROM DNA TO RNA
• Nucleotide Sequences Signal Where Splicing Occurs
Nucleotide Sequences Signal Where Splicing Occurs
FROM DNA TO RNA
• RNA Splicing Is Performed by the Spliceosome
El splicing de RNA está hecho por el spliceosoma
• Los pasos críticos en el procesamiento de RNA están hechos por
• moléculas de RNA- no por proteínas. Las moléculas de RNA reconocen las secuencias de nucleótidos que especifican los sitios de procesamiento y
también participan en la química del procesamiento (la catálisis).
• Son moléculas de RNA pequeñas (menos de 200nt) y 5 (U1, U2, U4, U5 y U6) son las que están involucradas en el tipo principal de splicing del pre-RNAm.
Son los snRNAs (RNAs pequeños nucleares), y cada uno forma un complejo con al menos 7 subunidades protéicas, y forman un snRNP (ribonucleoproteína
pequeña nuclear). Estas snRNPs forman la médula de spliceosoma, el complejo de RNA y proteínas que realiza el splicing.
RNA Splicing Is Performed by the Spliceosome
RNA Splicing Is Performed by the Spliceosome
RNA Splicing Is Performed by the Spliceosome
FROM DNA TO RNA
• The Spliceosome Uses ATP Hydrolysis to Produce a Complex Series of RNA–RNA Rearrangements
The Spliceosome Uses ATP Hydrolysis to Produce a Complex Series of RNA–RNA Rearrangements
FROM DNA TO RNA
• Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites
Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites
Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites
Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites
Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites
Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites
Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites
Other Properties of Pre-mRNA and Its Synthesis Help to Explain the Choice of Proper Splice Sites
FROM DNA TO RNA
• Chromatin Structure Affects RNA Splicing
FROM DNA TO RNA
• RNA Splicing Shows Remarkable Plasticity
RNA Splicing Shows Remarkable Plasticity
FROM DNA TO RNA
• Spliceosome-Catalyzed RNA Splicing Probably Evolved from Self-splicing Mechanisms
FROM DNA TO RNA
• RNA-Processing Enzymes Generate the 3ʹ End of
Eukaryotic mRNAs
RNA-Processing Enzymes Generate the 3ʹ End of Eukaryotic mRNAs
RNA-Processing Enzymes Generate the 3ʹ End of Eukaryotic mRNAs
RNA-Processing Enzymes Generate the 3ʹ End of Eukaryotic mRNAs
RNA-Processing Enzymes Generate the 3ʹ End of Eukaryotic mRNAs
FROM DNA TO RNA
• Mature Eukaryotic mRNAs Are Selectively Exported from the Nucleus
Mature Eukaryotic mRNAs Are Selectively Exported from the Nucleus
Mature Eukaryotic mRNAs Are Selectively Exported from the Nucleus
Mature Eukaryotic mRNAs Are Selectively Exported from the Nucleus
Mature Eukaryotic mRNAs Are Selectively Exported from the Nucleus
Mature Eukaryotic mRNAs Are Selectively Exported from the Nucleus
FROM DNA TO RNA
• Noncoding RNAs Are Also Synthesized and Processed in the Nucleus
Noncoding RNAs Are Also Synthesized and Processed in the Nucleus
Noncoding RNAs Are Also Synthesized and Processed in the Nucleus
Noncoding RNAs Are Also Synthesized and Processed in the Nucleus
Noncoding RNAs Are Also Synthesized and Processed in the Nucleus
Noncoding RNAs Are Also Synthesized and Processed in the Nucleus
FROM DNA TO RNA
• The Nucleolus Is a Ribosome-Producing Factory
The Nucleolus Is a Ribosome-Producing Factory
The Nucleolus Is a Ribosome-Producing Factory
The Nucleolus Is a Ribosome-Producing Factory
The Nucleolus Is a Ribosome-Producing Factory
The Nucleolus Is a Ribosome-Producing Factory
The Nucleolus Is a Ribosome-Producing Factory
FROM DNA TO RNA
• The Nucleus Contains a Variety of Subnuclear Aggregates
The Nucleus Contains a Variety of Subnuclear Aggregates
The Nucleus Contains a Variety of Subnuclear Aggregates
The Nucleus Contains a Variety of Subnuclear Aggregates
The Nucleus Contains a Variety of Subnuclear Aggregates
The Nucleus Contains a Variety of Subnuclear Aggregates
FROM RNA TO PROTEIN
• An mRNA Sequence Is Decoded in Sets of Three Nucleotides
An mRNA Sequence Is Decoded in Sets of Three Nucleotides
An mRNA Sequence Is Decoded in Sets of Three Nucleotides
FROM RNA TO PROTEIN
• tRNA Molecules Match Amino Acids to Codons in mRNA
tRNA Molecules Match Amino Acids to Codons in mRNA
tRNA Molecules Match Amino Acids to Codons in mRNA
tRNA Molecules Match Amino Acids to Codons in mRNA
tRNA Molecules Match Amino Acids to Codons in mRNA
tRNA Molecules Match Amino Acids to Codons in mRNA
tRNA Molecules Match Amino Acids to Codons in mRNA
tRNA Molecules Match Amino Acids to Codons in mRNA
FROM RNA TO PROTEIN
• tRNAs Are Covalently Modified Before They Exit from the Nucleus
tRNAs Are Covalently Modified Before They Exit from the Nucleus
tRNAs Are Covalently Modified Before They Exit from the Nucleus
FROM RNA TO PROTEIN
• Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule
Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule
Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule
Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule
Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule
Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule
FROM RNA TO PROTEIN
• Editing by tRNA Synthetases Ensures Accuracy
Editing by tRNA Synthetases Ensures Accuracy
Editing by tRNA Synthetases Ensures Accuracy
Editing by tRNA Synthetases Ensures Accuracy
Editing by tRNA Synthetases Ensures Accuracy
FROM RNA TO PROTEIN
• Amino Acids Are Added to the C-terminal End of a Growing Polypeptide Chain
Amino Acids Are Added to the C-terminal End of a Growing Polypeptide Chain
FROM RNA TO PROTEIN
• The RNA Message Is Decoded in Ribosomes
The RNA Message Is Decoded in Ribosomes
The RNA Message Is Decoded in Ribosomes
The RNA Message Is Decoded in Ribosomes
The RNA Message Is Decoded in Ribosomes
The RNA Message Is Decoded in Ribosomes
The RNA Message Is Decoded in Ribosomes
The RNA Message Is Decoded in Ribosomes
FROM RNA TO PROTEIN
• Elongation Factors Drive Translation Forward and Improve Its Accuracy
Elongation Factors Drive Translation Forward and Improve Its Accuracy
Elongation Factors Drive Translation Forward and Improve Its Accuracy
Elongation Factors Drive Translation Forward and Improve Its Accuracy
Elongation Factors Drive Translation Forward and Improve Its Accuracy
FROM RNA TO PROTEIN
• Many Biological Processes Overcome the Inherent Limitations of Complementary Base-Pairing
FROM RNA TO PROTEIN
• Accuracy in Translation Requires an Expenditure of Free Energy
FROM RNA TO PROTEIN
• The Ribosome Is a Ribozyme
The Ribosome Is a Ribozyme
The Ribosome Is a Ribozyme
The Ribosome Is a Ribozyme
The Ribosome Is a Ribozyme
The Ribosome Is a Ribozyme
FROM RNA TO PROTEIN
• Nucleotide Sequences in mRNA Signal Where to Start Protein Synthesis
Nucleotide Sequences in mRNA Signal Where to Start Protein Synthesis
Nucleotide Sequences in mRNA Signal Where to Start Protein Synthesis
Nucleotide Sequences in mRNA Signal Where to Start Protein Synthesis
Nucleotide Sequences in mRNA Signal Where to Start Protein Synthesis
FROM RNA TO PROTEIN
• Stop Codons Mark the End of Translation
Stop Codons Mark the End of Translation
FROM RNA TO PROTEIN
• Proteins Are Made on Polyribosomes
Proteins Are Made on Polyribosomes
Proteins Are Made on Polyribosomes
Proteins Are Made on Polyribosomes
FROM RNA TO PROTEIN
• There Are Minor Variations in the Standard Genetic Code
There Are Minor Variations in the Standard Genetic Code
FROM RNA TO PROTEIN
• Inhibitors of Prokaryotic Protein Synthesis Are Useful as Antibiotics
Inhibitors of Prokaryotic Protein Synthesis Are Useful as Antibiotics
Inhibitors of Prokaryotic Protein Synthesis Are Useful as Antibiotics
FROM RNA TO PROTEIN
• Quality Control Mechanisms Act to Prevent Translation of Damaged mRNAs
Quality Control Mechanisms Act to Prevent Translation of Damaged mRNAs
FROM RNA TO PROTEIN
• Some Proteins Begin to Fold While Still Being Synthesized
Some Proteins Begin to Fold While Still Being Synthesized
Some Proteins Begin to Fold While Still Being Synthesized
Some Proteins Begin to Fold While Still Being Synthesized
FROM RNA TO PROTEIN
• Molecular Chaperones Help Guide the Folding of Most Proteins
FROM RNA TO PROTEIN
• Cells Utilize Several Types of Chaperones
Cells Utilize Several Types of Chaperones
Cells Utilize Several Types of Chaperones
Cells Utilize Several Types of Chaperones
Cells Utilize Several Types of Chaperones
FROM RNA TO PROTEIN
• Exposed Hydrophobic Regions Provide Critical Signals for Protein Quality Control
Exposed Hydrophobic Regions Provide Critical Signals for Protein Quality Control
FROM RNA TO PROTEIN
• The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites
The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites
The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites
The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites
The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites
The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites
The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites
The Proteasome Is a Compartmentalized Protease with Sequestered Active Sites
FROM RNA TO PROTEIN
• Many Proteins Are Controlled by Regulated Destruction
Many Proteins Are Controlled by Regulated Destruction
Many Proteins Are Controlled by Regulated Destruction
Many Proteins Are Controlled by Regulated Destruction
FROM RNA TO PROTEIN
• There Are Many Steps From DNA to Protein
There Are Many Steps From DNA to Protein
THE RNA WORLD AND THEORIGINS OF LIFE
• Introduction
Introduction
THE RNA WORLD AND THEORIGINS OF LIFE
• Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures
Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures
Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures
Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures
Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures
Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures
Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures
THE RNA WORLD AND THEORIGINS OF LIFE
• RNA Can Both Store Information and Catalyze Chemical Reactions
RNA Can Both Store Information and Catalyze Chemical Reactions
THE RNA WORLD AND THEORIGINS OF LIFE
• How Did Protein Synthesis Evolve?
THE RNA WORLD AND THEORIGINS OF LIFE
• All Present-Day Cells Use DNA as Their Hereditary Material
All Present-Day Cells Use DNA as Their Hereditary Material
PROBLEMS
PROBLEMS
PROBLEMS
PROBLEMS
PROBLEMS
PROBLEMS