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

FROM DNA TO RNA

• Introduction

Introduction

FROM DNA TO RNA

• 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

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

FROM DNA TO RNA

• 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.


Secuencias consenso que se han encontrado cerca del inicio de la transcripción

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

FROM DNA TO RNA

• 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


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

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

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

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

FROM DNA TO RNA

• 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

FROM DNA TO RNA

• 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

FROM RNA TO PROTEIN

• 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

FROM RNA TO PROTEIN

• 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

FROM RNA TO PROTEIN

• 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

FROM RNA TO PROTEIN

• 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

FROM RNA TO PROTEIN

• 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

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

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

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

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

FROM RNA TO PROTEIN

• 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


• Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures

Single-Stranded RNA Molecules Can Fold into Highly Elaborate Structures


• RNA Can Both Store Information and Catalyze Chemical Reactions

RNA Can Both Store Information and Catalyze Chemical Reactions


• How Did Protein Synthesis Evolve?


• All Present-Day Cells Use DNA as Their Hereditary Material

All Present-Day Cells Use DNA as Their Hereditary Material

PROBLEMS

Transcripción Alberts 2014.pdf

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