Transcription

What is transcription?

Transcription is the synthesis of any type of complimentary RNA from a DNA template: note, several types of RNA can be encoded by a DNA strand [see DNA vs. RNA list]. Here, we focus specifically on transcription that leads to pre-mRNA, mRNA and eventually proteins. 

In the process of gene expression, transcription involves the production of messenger RNA (mRNA) from a DNA template. It takes place in the nucleus of a cell and is catalyzed by the enzyme RNA polymerase II.

RNA polymerase  All eukaryotes have three different types of RNA polymerase

RNA polymerase I transcribes rRNA genes

RNA polymerase II transcribes mRNA, miRNA, snRNA, and snRNA genes

RNA polymerase III transcribes an array of RNA genes, including but not limited to tRNA and 5S rRNA gene

 

 

 

 

 

The steps of transcription

The process of transcription entails several steps: 

1. Initiation

The first step of transcription to form mRNA involves RNA polymerase II binding to a promoter region  just upstream of the gene that is to be transcribed. Promoters are often classified as strong or weak based on their effects on transcription rates and thus gene expression. Transcription factors are proteins that help to position RNA polymerase II and assist in the breaking of the hydrogen bonds in the DNA helix. ³

2. Elongation

RNA polymerase II breaks the hydrogen bonds connecting two strands of DNA in the double helix. The enzyme then uses the single DNA strand as a template to build an RNA strand in the 5' to 3' direction, adding each complementary nucleotide to the 3' end of the strand. In RNA, the nucleotide thymine is replaced by the nucleotide uracil.³ 

What do we mean by 5' and 3'? This refers to the carbon numbers in DNA and RNA's backbone. The 5' carbon ribose ring frequently has a phosphate group attached, and the 3' carbon end has a hydroxyl (-OH) group attached. The asymmetry gives the DNA and RNA strands a "direction

The DNA strand moves through the RNA polymerase II enzyme. In the region behind where the nucleotides are being added to form the pre-mRNA strand, the DNA helix re-forms. This means that the pre-mRNA produced is eventually released from the DNA template a single strand. 

3. Termination

Termination marks the end of RNA polymerase II adding nucleotides to the pre-mRNA strand and the release of the pre-mRNA. Despite extensive research, there is still ambiguity surrounding the precise physiological cause of termination - several mechanisms are outlined in this review paper .

From pre-mRNA to mRNA

Eukaryotic pre-mRNAs must go through several additional processing steps before translation can occur. Firstly, they have a 5' cap added and a 3' poly-A-tail added to protect against transcript degradation.⁴ 

Many eukaryotic pre-mRNAs are subject to splicing. Here, the non-coding sections of the pre-mRNA (introns) are cut out, and the coding sections (the exons) are effectively glued back together.

Schematic showing pre-mRNA undergoing splicing to form mature mRNA.  

Alternative splicing may also take place, whereby exons or noncoding regions within the pre-Mrna transcript are joined or skipped, resulting in multiple mRNAs being encoded by a single gene.

After these modifications have taken place, the resulting strand is known as mature mRNA. This mature mRNA is then able to leave the nucleus and enter the cell cytoplasm where translation takes place. 

 

Neuroglia, Astrocyte lecture note

The dorsal column–medial lemniscus pathway

The dorsal column–medial lemniscus pathway (DCML) (also known as the posterior column-medial lemniscus pathway, PCML) is a sensory pathway of the central nervous system that conveys sensations of fine touch, vibration, two-point discrimination, and proprioception(position) from the skin and joints. It transmits information from the body to the primary somatosensory cortex in the postcentral gyrus of the parietal lobe of the brain.

 The pathway receives information from sensory receptors (missner’s corpuscle, pacinian corpuscle etc.) throughout the body, and carries this in nerve tracts in the white matter of the dorsal columns of the spinal cord to the medulla, where it is continued in the medial lemniscuses, on to the thalamus and relayed from there through the internal capsule and transmitted to the somatosensory cortex.

The name dorsal-column medial lemniscus comes from the two structures that carry the sensory information: the dorsal columns of the spinal cord, and the medial lemniscus in the brainstem.

There are three groupings of neurons that are involved in the pathway: first-order neurons, second-order neurons, and third-order neurons.

 The first-order neurons are sensory neurons located in the dorsal root ganglia, that send their afferent fibers through the two dorsal columns – the gracile fasciculus, or gracile tract, and the cuneate fasciculus, or cuneate tract. The first-order axons make contact with second-order neurons of the dorsal column nuclei (the gracile nucleus and the cuneate nucleus) in the lower medulla.

The second-order neurons send their axons to the thalamus.

The third-order neurons are in the ventral nuclear group in the thalamus and fibres from these ascend to the postcentral gyrus.

Sensory information from the upper half of the body is received at the cervical level of the spinal cord and carried in the cuneate tract, and information from the lower body is received at the lumbar level and carried in the gracile tract. The gracile tract is medial to the more lateral cuneate tract.

The axons of second-order neurons of the gracile and cuneate nuclei are known as the internal arcuate fibers and when they cross over the midline, at the sensory decussation in the medulla, they form the medial lemniscus which connects with thalamus; the axons synapse on neurons in the ventral nuclear group which then send axons to the postcentral gyrus in the parietal lobe. All of the axons in the DCML pathway are rapidly conducting, large, myelinated fibers.

 

Lateral spinothalamic tract

 

The lateral spinothalamic tract, also known as the lateral spinothalamic fasciculus, is an ascending pathway located anterolaterally within the peripheral white matter of the spinal cord. It is primarily responsible for transmitting pain and temperature as well as coarse touch. 

The anterior spinothalamic tract (discussed separately), in contrast, primarily transmits coarse touch and pressure. 

First-order neurons, whose cell bodies are in the dorsal root ganglion and whose axons extend from peripheral receptors, enter the cord via dorsal nerve roots. 

First-order neurons synapse with second-order neurons whose bodies are located in the ipsilateral substantia gelatinosa of dorsal horn of the spinal cord.

The lateral spinothalamic tract then ascends in the lateral funiculus, just medial to the ventral spinocerebellar tract. Fibers of this tract are somatotopically organized for their entire course.

Upon reaching the brainstem, the lateral and anterior spinothalamic tracts combine to form the spinal lemniscus, which runs lateral to the medial lemniscus

 The spinal lemniscus terminates in the ventral posterior nucleus of the thalamus. Here, it synapses with third-order neurons, which project to the primary somatosensory area on the ipsilateral side of the cerebral cortex.

Lesion : 

Contra-lateral loss of pain & thermal sensibilities below the level of the lesion

Unable to sense pin prick or recognize hot or cold objects 

Summary of Somatosensory pathways: lateral & anterior spinothalamic tract and tract of gall and cuneatus

Summary of Somatosensory pathways

The somatosensory system is a part of the sensory nervous system.

It  is a complex system of sensory neurons and neural pathways that responds to changes at the external environment or inside the body.

The axons (as afferent nerve fibers) of sensory neurons has two part peripheral and center part. Terminal portion of peripheral portion of axon of sensory neuron is converted into receptors.

 Sensory receptors are found all over the body including the skin, epithelial tissues, muscles, bones and joints, internal organs, and the cardiovascular system.

Touch is a crucial means of receiving information. This photo shows tactile markings identifying stairs for visually impaired people.

Somatic senses are sometimes referred to as somesthetic senses, with the understanding that somesthesis includes the sense of touch, proprioception (sense of position and movement), and (depending on usage) haptic perception

The mapping of the body surfaces in the brain is called somatotopy. In the cortex, it is also referred to as the cortical homunculus. This brain-surface ("cortical") map is not immutable, however. Dramatic shifts can occur in response to stroke or injury.

Our nervous system deal two types of sensation conscious and unconscious . this article summarized the main somatosensory pathways 

Topics	Lateral spino-thalamic tract	Anterior spinothalamic tract	Tract of gracilis & cuneatus
Sensation	Pain and temperature	Light touch and pressure	Discriminative touch, vibration , conscious muscle joint sense
Receptor	Free nerve ending	Free nerve ending	Meissners corpuscles, pacinian corpuscles, muscle spindles , tendon organ
1st order neuron	Posterior root ganglion	Posterior root ganglion	Posterior root ganglion
2nd order neuron	Substantia getalinosa	Substantia getalinosa	Nuclei gracilis and nuceatus
3rd order neuron	Ventral posterior lateral nucleus of thalamus	Ventral posterior lateral nucleus of thalamus	Ventral posterior lateral nucleus of thalamus
Related with Spinal lamniscus	Present	Present	Absent
Related with Medial lamniscus	Absent	Absent	Present
Destination	Post central gyrus	Post central gyrus	Post central gyrus
Lesion	Contra-lateral loss of pain and thermal sensibilities below the level of the lesion Unable to sense pin prick or recognize hot or cold objects	Contra-lateral loss of light touch and pressure  sensibilities below the level of the lesion. Discriminative touch will be present but unable to feel light touch of cotton placed against the skin	Ipsilateral loss of muscle and joint sensation, two point discrimination and vibration  below the level of lesion but sense of light touch is unaffected Movement are jerky or ataxic